Liddle综合征表型和基因型关系分析及基于中国北方汉族人群药物基因组学的华法林维持剂量公式建立
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摘要
背景：Liddle综合征是一种常染色体显性遗传疾病,由上皮钠通道的基因突变导致。已报道的Liddle综合征患者中,绝大多数均因错义突变或移码框架突变而导致位于上皮钠通道p或γ亚基羧基末端保守的富含脯氨基酸的PY模体发生缺失或改变。Liddle综合征的典型表现为早发的低钾性高血压,并伴随血浆低肾素活性和低醛固酮水平,但临床上,不同患者血压水平、血浆钾浓度和其它临床特征均表现出很大的表型异质性。
目标：通过两个Liddle综合征中国家庭分析基因型与表型的关系。
方法：收集疑似Liddle综合征的两个患者及其家庭成员的临床资料,并对编码上皮钠通道β亚基的SCNN1B基因和编码γ亚基的SCNN1G基因羧基端进行测序。其中一个家庭除了高血压和低血钾外,曾有家庭成员发生猝死,所以对此家庭成员进行了额外的428个心血管疾病相关基因的全外显子测序。检测到上皮钠通道基因突变后,与既往研究中携带同样突变的患者表型进行比较和分析。
结果：先证者1所在家庭中,先证者1及其姐姐、父亲均检出杂合的无义突变βR566X。他们都有高血压低血钾,但程度较轻,血压也可通过钙通道阻滞剂联合上皮钠通道阻滞剂很好地控制。在既往的4个对βR566X的报道中,其中2个报道中的携带者表型较轻,与本文类似；但另外2个报道中携带者却有严重的表型,包括早发卒中和死亡等。在先证者2家系中所发现的杂合βR597PfrX607移码框架突变则带来了严重恶性的表型,包括难以控制的高血压、低钾、严重的靶器官损害,并且先证者2及其父亲均在20余岁时发生猝死。但在既往的报道中pR597PfrX607突变仅引起中等程度的表型,患者血压可用上皮钠通道阻滞剂单药控制,并且无早发恶性心血管事件家族史。在另外进行外显子扫描的428个心血管疾病相关的基因中,除了SCNN1B外,一些错义突变或移码框架突变也被发现,但它们大多同样存在于先证者2正常表型的兄长。先证者2独有的几个突变所在基因尚无功能实验或者清晰的相关性实验证明其与血压相关。
结论：即使携带同样的突变,Liddle综合征的表型变异也很显著。同样的突变导致不同表型的机制值得更深入的研究,对调节因素进行干预可能改善疾病的病程和预后。
背景：目前华法林仍然是预防和治疗血栓栓塞的主要口服抗凝药,但由于其治疗窗狭窄、个体反应差异大,对华法林治疗剂量的控制仍然面临挑战。华法林的作用受到很多因素的影响,包括性别、年龄、体表面积、服用的其它药物和食物等。同时华法林的作用也受到基因因素的调控。既往已经有许多研究表明基因CYP2C9和VKORCl内的单核酸多态性位点与华法林剂量相关,基因CYP4F2中的位点rs2108622(V433M)也曾被报道与华法林剂量相关。美国食品和药物管理局已明确提出,“患者的CYP2C9和VKORC1基因型,可以协助选择华法林起始剂量”。既往研究已经在中国人中建立了一些预测华法林剂量的公式,但普遍样本量小,仅有的两个较大的中国汉族人群华法林维持剂量的研究分别在中国的南部和中部展开。
目的：本研究旨在中国北方居住人群中评估影响华法林维持剂量的基因并建立一个整合基因和常见干扰因素的公式用于预测华法林维持剂量。
方法：顺序纳入800个因心脏瓣膜置换术需要长期华法林维持治疗的患者,对他们进行了23个相关单核苷酸多态性位点的基因分型。首先检测这些单核苷酸多态性位点与华法林维持剂量的关系,在先证队列(总体队列的70%人群)中,基于基因型与华法林维持剂量的关系,建立一个整合了常见非基因因素的维持剂量计算公式,并在验证队列(总体队列的30%人群)中对公式进行评估。
结果：基因VKORC1和CYP2C9的单核苷酸多态性位点显示出与华法林剂量的显著相关性。基因CYP4F2中rs2108622位点在单因素分析中与华法林剂量关联未达显著意义(P=0.152),但最终的多因素回归模型中P值变为0.01。总的来说,在初始队列(n=551)中,华法林剂量在不同程度上被多个因素影响,VKORC1rs7294(27.3%),CYP2C9*3(7.0%),体表面积(4.2%),年龄(2.7%),目标INR值(1.4%),CYP4F2rs2108622(0.7%),氨碘酮使用(0.6%),糖尿病(0.6%)以及地高辛使用(0.5%),总共约45.1%的华法林剂量变异可由以上因素解释。在验证队列(n=236)中,实际维持剂量与预测剂量显著相关(r=0.609,P<0.001)。另外,相较于中国南方公式和中部公式,我们的公式对中国北方人群华法林维持剂量的预测最为准确。
结论：本研究建立的公式可能帮助中国北方患者更有效地进行个体华法林剂量管理。
Background:Liddle syndrome is an autosomal-dominant inheritance disease, caused by mutations in an epithelial sodium channel (ENaC). Most reported mutations in patients with Liddle syndrome are either missense or frameshift mutations that either delete or alter the conserved proline-rich PY motif (PPPXY sequence) localized at the C-terminal ends of the β and γ subunits of ENaC. Typical Liddle syndrome is characterized by early onset of hypokalemic hypertension with low plasma renin activity (PRA) and low serum aldosterone level, but patients with Liddle syndrome show marked phenotypic variation in blood pressure, serum potassium and other clinical manifestations.
Objective:Analyzed the correlation of genotype-phenotype in two Chinese families with Liddle syndrome.
Methods:The sequence of C-terminus of SCNN1B and SCNN1G were screened in the two families with likely Liddle syndrome, and there clinical information were collected. In addition to hypertension and hypokalemia, one of the two pedigrees had sudden death in their family members, so the exons of428reported genes-related to cardiovascular diseases were screened as well in the family. We also compared the phenotypes among the patients carrying the identical mutation in our study and in previous studies
Results:A heterozygous PR566X nonsense mutation was found in the proband-1in the first pedigree, and the proband's sister and father. They showed mild phenotype with hypertension and hypokalemia, and the blood pressure was under control by calcium channel bloker and ENac blocker. Two of the four previous studies report that the mutation causes severe phenotype, even die of stroke in their thirties, while the other two families showed a mild clinical phenotype. In contrast, a heterozygous pR597PfrX607frameshift mutation was identified in the proband-2in the second pedigree, showing malignant phenotype including resistant hypertension, hypokalemia, and sever target organ damagement. Both the proband-2and the proband-2's father had sudden death in their twenties. But the same mutation has been related to moderate phenotype in previous studies, in which blood pressure could been controlled by ENaC blocker and no early maglinant cardiovascular events. By screening of the exons in428cardiovascular disease-related genes, some missense and frameshift mutations were found other than SCNN1B, but most of them were also detected in the proband's brother, who was a genetically unaffected member with normal phenotype. Genes with mutation-unique to the proband-2has not been associated with blood pressure by either function study or convincable association study.
Conclusion:The phenotypes of Liddle syndrome are varied significantly even with the same mutation. The mechanisms why the same mutation causes very different phenotype need to be explored because intervention of these modifiers may change the disease course and prognosis accordingly.
Background:Warfarin has remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. However, management of warfarin therapy is challenging because of its narrow therapeutic index and wide inter-individual variability. Effect of warfarin could be influenced by many factors, incluing gender, age, body surface area, concominant drugs and foods. Also genetic variants could affect warfarin, many studies have shown that single nucleotide polymorphisms (SNPs) within CYP2C9and VKORC1genes are related to warfarin dose requirement. CYP4F2rs2108622(V433M) was found to be associated with warfarin dose in3independent Caucasian cohorts. Food and Drug Administration has changed the drug label for warfarin and include the statement,"The patient's CYP2C9and VKORC1genotype information, when available, can assist in selection of the starting dose." Previous studies constructed many algorithms to predict the warfarin maintenance dose in Chinese individuals. However, they frequently used relatively small populations (<400subjects) except in two studies where one included845from Southern China, and the other included641from Central China
Objectives:The objective of the current study was to assess these genetic determinants of the warfarin maintenance dose and to construct an algorithm integrating common interference factors to predict the dose in a large population who lived in Northern China.
Methods:This study enrolled800consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy,23related SNPs were genotyped. First, the associations of these SNPs with the warfarin maintenance dose were tested. Second, on the basis of genotypes associated with the warfarin maintenance dose, an algorithm integrating common non-genetic factors was constructed to predict the dose in the derivation cohort (70%of the whole cohort), and was assessed in the validation cohort (30%of the whole cohort).
Results:Only VKORC1and CYP2C9SNPs were observed to be significantly associated with warfarin dose. The relationship between gene CYP4F2rs2108622and warfarin dose was not significant in the univariate analysis(P=0.152), however, the P-value was0.01in the final multiple regression model. Generally, in the derivation cohort (n=551), warfarin dose variability was influenced, in decreasing order, by VKORC1rs7294(27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2rs2108622(0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for45.1%of the warfarin dose variability. In the validation cohort (n=236), the actual maintenance dose was significantly correlated with predicted dose (r=0.609, P<0.001). Furthermore, our algorithm demonstrated the best predictor in northern Chinese people compared with the other two algorithms derived from southern Chinese and central Chinese populations.
Conclusions:Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients.
目标：通过两个Liddle综合征中国家庭分析基因型与表型的关系。
方法：收集疑似Liddle综合征的两个患者及其家庭成员的临床资料,并对编码上皮钠通道β亚基的SCNN1B基因和编码γ亚基的SCNN1G基因羧基端进行测序。其中一个家庭除了高血压和低血钾外,曾有家庭成员发生猝死,所以对此家庭成员进行了额外的428个心血管疾病相关基因的全外显子测序。检测到上皮钠通道基因突变后,与既往研究中携带同样突变的患者表型进行比较和分析。
结果：先证者1所在家庭中,先证者1及其姐姐、父亲均检出杂合的无义突变βR566X。他们都有高血压低血钾,但程度较轻,血压也可通过钙通道阻滞剂联合上皮钠通道阻滞剂很好地控制。在既往的4个对βR566X的报道中,其中2个报道中的携带者表型较轻,与本文类似；但另外2个报道中携带者却有严重的表型,包括早发卒中和死亡等。在先证者2家系中所发现的杂合βR597PfrX607移码框架突变则带来了严重恶性的表型,包括难以控制的高血压、低钾、严重的靶器官损害,并且先证者2及其父亲均在20余岁时发生猝死。但在既往的报道中pR597PfrX607突变仅引起中等程度的表型,患者血压可用上皮钠通道阻滞剂单药控制,并且无早发恶性心血管事件家族史。在另外进行外显子扫描的428个心血管疾病相关的基因中,除了SCNN1B外,一些错义突变或移码框架突变也被发现,但它们大多同样存在于先证者2正常表型的兄长。先证者2独有的几个突变所在基因尚无功能实验或者清晰的相关性实验证明其与血压相关。
结论：即使携带同样的突变,Liddle综合征的表型变异也很显著。同样的突变导致不同表型的机制值得更深入的研究,对调节因素进行干预可能改善疾病的病程和预后。
背景：目前华法林仍然是预防和治疗血栓栓塞的主要口服抗凝药,但由于其治疗窗狭窄、个体反应差异大,对华法林治疗剂量的控制仍然面临挑战。华法林的作用受到很多因素的影响,包括性别、年龄、体表面积、服用的其它药物和食物等。同时华法林的作用也受到基因因素的调控。既往已经有许多研究表明基因CYP2C9和VKORCl内的单核酸多态性位点与华法林剂量相关,基因CYP4F2中的位点rs2108622(V433M)也曾被报道与华法林剂量相关。美国食品和药物管理局已明确提出,“患者的CYP2C9和VKORC1基因型,可以协助选择华法林起始剂量”。既往研究已经在中国人中建立了一些预测华法林剂量的公式,但普遍样本量小,仅有的两个较大的中国汉族人群华法林维持剂量的研究分别在中国的南部和中部展开。
目的：本研究旨在中国北方居住人群中评估影响华法林维持剂量的基因并建立一个整合基因和常见干扰因素的公式用于预测华法林维持剂量。
方法：顺序纳入800个因心脏瓣膜置换术需要长期华法林维持治疗的患者,对他们进行了23个相关单核苷酸多态性位点的基因分型。首先检测这些单核苷酸多态性位点与华法林维持剂量的关系,在先证队列(总体队列的70%人群)中,基于基因型与华法林维持剂量的关系,建立一个整合了常见非基因因素的维持剂量计算公式,并在验证队列(总体队列的30%人群)中对公式进行评估。
结果：基因VKORC1和CYP2C9的单核苷酸多态性位点显示出与华法林剂量的显著相关性。基因CYP4F2中rs2108622位点在单因素分析中与华法林剂量关联未达显著意义(P=0.152),但最终的多因素回归模型中P值变为0.01。总的来说,在初始队列(n=551)中,华法林剂量在不同程度上被多个因素影响,VKORC1rs7294(27.3%),CYP2C9*3(7.0%),体表面积(4.2%),年龄(2.7%),目标INR值(1.4%),CYP4F2rs2108622(0.7%),氨碘酮使用(0.6%),糖尿病(0.6%)以及地高辛使用(0.5%),总共约45.1%的华法林剂量变异可由以上因素解释。在验证队列(n=236)中,实际维持剂量与预测剂量显著相关(r=0.609,P<0.001)。另外,相较于中国南方公式和中部公式,我们的公式对中国北方人群华法林维持剂量的预测最为准确。
结论：本研究建立的公式可能帮助中国北方患者更有效地进行个体华法林剂量管理。
Background:Liddle syndrome is an autosomal-dominant inheritance disease, caused by mutations in an epithelial sodium channel (ENaC). Most reported mutations in patients with Liddle syndrome are either missense or frameshift mutations that either delete or alter the conserved proline-rich PY motif (PPPXY sequence) localized at the C-terminal ends of the β and γ subunits of ENaC. Typical Liddle syndrome is characterized by early onset of hypokalemic hypertension with low plasma renin activity (PRA) and low serum aldosterone level, but patients with Liddle syndrome show marked phenotypic variation in blood pressure, serum potassium and other clinical manifestations.
Objective:Analyzed the correlation of genotype-phenotype in two Chinese families with Liddle syndrome.
Methods:The sequence of C-terminus of SCNN1B and SCNN1G were screened in the two families with likely Liddle syndrome, and there clinical information were collected. In addition to hypertension and hypokalemia, one of the two pedigrees had sudden death in their family members, so the exons of428reported genes-related to cardiovascular diseases were screened as well in the family. We also compared the phenotypes among the patients carrying the identical mutation in our study and in previous studies
Results:A heterozygous PR566X nonsense mutation was found in the proband-1in the first pedigree, and the proband's sister and father. They showed mild phenotype with hypertension and hypokalemia, and the blood pressure was under control by calcium channel bloker and ENac blocker. Two of the four previous studies report that the mutation causes severe phenotype, even die of stroke in their thirties, while the other two families showed a mild clinical phenotype. In contrast, a heterozygous pR597PfrX607frameshift mutation was identified in the proband-2in the second pedigree, showing malignant phenotype including resistant hypertension, hypokalemia, and sever target organ damagement. Both the proband-2and the proband-2's father had sudden death in their twenties. But the same mutation has been related to moderate phenotype in previous studies, in which blood pressure could been controlled by ENaC blocker and no early maglinant cardiovascular events. By screening of the exons in428cardiovascular disease-related genes, some missense and frameshift mutations were found other than SCNN1B, but most of them were also detected in the proband's brother, who was a genetically unaffected member with normal phenotype. Genes with mutation-unique to the proband-2has not been associated with blood pressure by either function study or convincable association study.
Conclusion:The phenotypes of Liddle syndrome are varied significantly even with the same mutation. The mechanisms why the same mutation causes very different phenotype need to be explored because intervention of these modifiers may change the disease course and prognosis accordingly.
Background:Warfarin has remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. However, management of warfarin therapy is challenging because of its narrow therapeutic index and wide inter-individual variability. Effect of warfarin could be influenced by many factors, incluing gender, age, body surface area, concominant drugs and foods. Also genetic variants could affect warfarin, many studies have shown that single nucleotide polymorphisms (SNPs) within CYP2C9and VKORC1genes are related to warfarin dose requirement. CYP4F2rs2108622(V433M) was found to be associated with warfarin dose in3independent Caucasian cohorts. Food and Drug Administration has changed the drug label for warfarin and include the statement,"The patient's CYP2C9and VKORC1genotype information, when available, can assist in selection of the starting dose." Previous studies constructed many algorithms to predict the warfarin maintenance dose in Chinese individuals. However, they frequently used relatively small populations (<400subjects) except in two studies where one included845from Southern China, and the other included641from Central China
Objectives:The objective of the current study was to assess these genetic determinants of the warfarin maintenance dose and to construct an algorithm integrating common interference factors to predict the dose in a large population who lived in Northern China.
Methods:This study enrolled800consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy,23related SNPs were genotyped. First, the associations of these SNPs with the warfarin maintenance dose were tested. Second, on the basis of genotypes associated with the warfarin maintenance dose, an algorithm integrating common non-genetic factors was constructed to predict the dose in the derivation cohort (70%of the whole cohort), and was assessed in the validation cohort (30%of the whole cohort).
Results:Only VKORC1and CYP2C9SNPs were observed to be significantly associated with warfarin dose. The relationship between gene CYP4F2rs2108622and warfarin dose was not significant in the univariate analysis(P=0.152), however, the P-value was0.01in the final multiple regression model. Generally, in the derivation cohort (n=551), warfarin dose variability was influenced, in decreasing order, by VKORC1rs7294(27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2rs2108622(0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for45.1%of the warfarin dose variability. In the validation cohort (n=236), the actual maintenance dose was significantly correlated with predicted dose (r=0.609, P<0.001). Furthermore, our algorithm demonstrated the best predictor in northern Chinese people compared with the other two algorithms derived from southern Chinese and central Chinese populations.
Conclusions:Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients.
引文
[1]Chan L., Boerwinkle E. Gene-Environment Interactions and Gene Therapy in Atherosclerosis [J]. Cardiology in Review,1994,2(3):130-137.
[2]Feinleib M., Garrison R. J., Fabsitz R., et al. The NHLBI twin study of cardiovascular disease risk factors:methodology and summary of results [J]. American journal of epidemiology,1977,106(4):284-285.
[3]Mongeau J. G, Biron P., Sing C. F. The influence of genetics and household environment upon the variability of normal blood pressure:the Montreal Adoption Survey [J]. Clinical and experimental hypertension Part A, Theory and practice,1986, 8(4-5):653-660.
[4]Manolio T. A., Collins F. S., Cox N. J., et al. Finding the missing heritability of complex diseases [J]. Nature,2009,461(7265):747-753.
[5]Newton-Cheh C., Johnson T., Gateva V., et al. Genome-wide association study identifies eight loci associated with blood pressure [J]. Nature genetics,2009,41(6): 666-676.
[6]Levy D., Ehret G. B., Rice K., et al. Genome-wide association study of blood pressure and hypertension [J]. Nature genetics,2009,41(6):677-687.
[7]Kato N., Takeuchi F., Tabara Y., et al. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians [J]. Nature genetics,2011,43(6):531-538.
[8]Ehret G. B., Munroe P. B., Rice K. M., et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk [J]. Nature,2011,478(7367): 103-109.
[9]Wain L. V., Verwoert G. C., O'reilly P. F., et al. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure [J]. Nature genetics,2011,43(10):1005-1011.
[10]Liddle G. W., Bledsoe T., Coppage W. S. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. [J]. Trans Assoc Am Physicians 1963,76(199-213.
[11]Takahashi H., Ieiri I., Wilkinson G. R., et al.5'-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients [J]. Blood,2004,103(8):3055-3057.
[12]Zhao F., Loke C., Rankin S. C., et al. Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose [J]. Clinical pharmacology and therapeutics,2004,76(3):210-219.
[13]Yuan H. Y., Chen J. J., Lee M. T., et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity [J]. Human molecular genetics,2005,14(13):1745-1751.
[14]Veenstra D. L., You J. H., Rieder M. J., et al. Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population [J]. Pharmacogenetics and genomics,2005,15(10):687-691.
[15]Tham L. S., Goh B. C., Nafziger A., et al. A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9 [J]. Clinical pharmacology and therapeutics,2006,80(4): 346-355.
[16]Miao L., Yang J., Huang C., et al. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin:proposal for a new dosing regimen in Chinese patients [J]. European journal of clinical pharmacology,2007, 63(12):1135-1141.
[17]Wen M. S., Lee M., Chen J. J., et al. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes [J]. Clinical pharmacology and therapeutics,2008,84(1):83-89.
[18]Huang S. W., Chen H. S., Wang X. Q., et al. Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose:a prospective study in Chinese patients [J]. Pharmacogenetics and genomics,2009,19(3):226-234.
[19]Lee M. T., Chen C. H., Chou C. H., et al. Genetic determinants of warfarin dosing in the Han-Chinese population [J]. Pharmacogenomics,2009,10(12):1905-1913.
[20]Lenzini P., Wadelius M., Kimmel S., et al. Integration of genetic, clinical, and INR data to refine warfarin dosing [J]. Clinical pharmacology and therapeutics,2010,87(5): 572-578.
[21]Sagreiya H., Berube C., Wen A., et al. Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9 [J]. Pharmacogenetics and genomics,2010,20(7):407-413.
[22]Gong I. Y., Schwarz U. I., Crown N., et al. Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation [J]. PloS one,2011,6(11):e27808.
[23]Caldwell M. D., Awad T., Johnson J. A., et al. CYP4F2 genetic variant alters required warfarin dose [J]. Blood,2008,111(8):4106-4112.
[24]Wei M., Ye F., Xie D., et al. A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and VKORC1 and clinical variables:derivation in Han Chinese patients with non valvular atrial fibrillation [J]. Thrombosis and haemostasis,2012,107(6):1083-1091.
[25]You J. H., Wong R. S., Waye M. M., et al. Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients [J]. Journal of thrombosis and thrombolysis,2011,31(1):113-118.
[26]Zhong S. L., Yu X. Y, Liu Y, et al. Integrating interacting drugs and genetic variations to improve the predictability of warfarin maintenance dose in Chinese patients [J]. Pharmacogenetics and genomics,2012,22(3):176-182.
[27]Tan S. L., Li Z., Song G. B., et al. Development and comparison of a new personalized warfarin stable dose prediction algorithm in Chinese patients undergoing heart valve replacement [J]. Die Pharmazie,2012,67(11):930-937.
[1]Liddle G. W., Bledsoe T., Coppage W. S. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. [J]. Trans Assoc Am Physicians 1963,76(199-213).
[2]Firsov D., Schild L., Gautschi I., et al. Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome:a quantitative approach [J]. Proceedings of the National Academy of Sciences of the United States of America,1996,93(26): 15370-15375.
[3]Hansson J. H., Schild L., Lu Y., et al. A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity [J]. Proceedings of the National Academy of Sciences of the United States of America,1995, 92(25):11495-11499.
[4]Canessa C. M., Schild L., Buell G, et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits [J]. Nature,1994,367(6462):463-467.
[5]Hiltunen T. P., Hannila-Handelberg T., Petajaniemi N., et al. Liddle's syndrome associated with a point mutation in the extracellular domain of the epithelial sodium channel gamma subunit [J]. J Hypertens,2002,20(12):2383-2390.
[6]Rayner B. L., Owen E. P., King J. A., et al. A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension [J]. Journal of hypertension,2003,21(5):921-926.
[7]Snyder P. M., Price M. P., Mcdonald F. J., et al. Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel [J]. Cell,1995, 83(6):969-978.
[8]Schild L., Lu Y., Gautschi I., et al. Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome [J]. The EMBO journal,1996,15(10):2381-2387.
[9]World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects [J]. JAMA,1997,277(11): 925-926.
[10]Shi J. Y., Chen X., Ren Y., et al. [Liddle's syndrome caused by a novel mutation of the gamma-subunit of epithelial sodium channel gene SCNN1G in Chinese] [J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2010,27(2):132-135.
[11]Shimkets R. A., Warnock D. G, Bositis C. M., et al. Liddle's syndrome:heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel [J]. Cell,1994,79(3):407-414.
[12]Kyuma M., Ura N., Torii T., et al. A family with liddle's syndrome caused by a mutation in the beta subunit of the epithelial sodium channel [J]. Clin Exp Hypertens, 2001,23(6):471-478.
[13]Melander O., Orho M., Fagerudd J., et al. Mutations and variants of the epithelial sodium channel gene in Liddle's syndrome and primary hypertension [J]. Hypertension, 1998,31(5):1118-1124.
[14]Inoue T., Okauchi Y, Matsuzaki Y, et al. Identification of a single cytosine base insertion mutation at Arg-597 of the beta subunit of the human epithelial sodium channel in a family with Liddle's disease [J]. Eur J Endocrinol,1998,138(6):691-697.
[15]Jackson S. N., Williams B., Houtman P., et al. The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel [J]. Journal of medical genetics,1998,35(6):510-512.
[16]Nakano Y, Ishida T., Ozono R., et al. A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome [J]. Journal of hypertension,2002,20(12):2379-2382.
[17]Jeunemaitre X., Bassilana F., Persu A., et al. Genotype-phenotype analysis of a newly discovered family with Liddle's syndrome [J]. J Hypertens,1997,15(10): 1091-1100.
[18]Hansson J. H., Nelson-Williams C., Suzuki H., et al. Hypertension caused by a truncated epithelial sodium channel gamma subunit:genetic heterogeneity of Liddle syndrome [J]. Nature genetics,1995,11(1):76-82.
[19]Wang W., Zhou W., Jiang L., et al. Mutation analysis of SCNN1B in a family with Liddle's syndrome [J]. Endocrine,2006,29(3):385-390.
[20]Inoue J., Iwaoka T., Tokunaga H., et al. A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel [J]. J Clin Endocrinol Metab,1998,83(6):2210-2213.
[21]Gao P. J., Zhang K. X., Zhu D. L., et al. Diagnosis of Liddle syndrome by genetic analysis of beta and gamma subunits of epithelial sodium channel--a report of five affected family members [J]. Journal of hypertension,2001,19(5):885-889.
[22]Yamashita Y., Koga M., Takeda Y., et al. Two sporadic cases of Liddle's syndrome caused by De novo ENaC mutations [J]. Am J Kidney Dis,2001,37(3):499-504.
[23]Uehara Y, Sasaguri M., Kinoshita A., et al. Genetic analysis of the epithelial sodium channel in Liddle's syndrome [J]. J Hypertens,1998,16(8):1131-1135.
[24]Freundlich M., Ludwig M. A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome [J]. Pediatr Nephrol,2005,20(4): 512-515.
[25]Tamura H., Schild L., Enomoto N., et al. Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene [J]. The Journal of clinical investigation,1996,97(7):1780-1784.
[26]Rossi E., Farnetti E., Debonneville A., et al. Liddle's syndrome caused by a novel missense mutation (P617L) of the epithelial sodium channel beta subunit [J]. J Hypertens, 2008,26(5):921-927.
[27]Sawathiparnich P., Sumboonnanonda A., Weerakulwattana P., et al. A novel mutation in the beta-subunit of the epithelial sodium channel gene (SCNN1B) in a Thai family with Liddle's syndrome [J]. J Pediatr Endocrinol Metab,2009,22(1):85-89.
[28]Gao L., Wang L., Liu Y, et al. A family with Liddle syndrome caused by a novel missense mutation in the PY motif of the beta-subunit of the epithelial sodium channel [J]. The Journal of pediatrics,2013,162(1):166-170.
[29]Wang Y., Zheng Y., Chen J., et al. A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome [J]. Clinical endocrinology,2007, 67(5):801-804.
[30]Jones E. S., Owen E. P., Davidson J. S., et al. The R563Q mutation of the epithelial sodium channel beta-subunit is associated with hypertension [J]. Cardiovascular journal of Africa,2011,22(5):241-244.
[31]Rossi E., Farnetti E., Nicoli D., et al. A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome [J]. American journal of hypertension,2011,24(8):930-935.
[32]Bertog M., Cuffe J. E., Pradervand S., et al. Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome [J]. The Journal of physiology,2008,586(2):459-475.
[33]Bogdanovic R., Kuburovic V., Stajic N., et al. Liddle syndrome in a Serbian family and literature review of underlying mutations [J]. European journal of pediatrics,2012, 171(3):471-478.
[34]Wang L. P., Gao L. G, Zhou X. L., et al. Genetic diagnosis of Liddle's syndrome by mutation analysis of SCNNIB and SCNNIG in a Chinese family [J]. Chinese medical journal,2012,125(8):1401-1404.
[35]Staub O., Gautschi I., Ishikawa T., et al. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination [J]. The EMBO journal,1997,16(21): 6325-6336.
[36]Lu C., Pribanic S., Debonneville A., et al. The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool [J]. Traffic,2007,8(9):1246-1264.
[37]Araki N., Umemura M., Miyagi Y., et al. Expression, transcription, and possible antagonistic interaction of the human Nedd4L gene variant:implications for essential hypertension [J]. Hypertension,2008,51(3):773-777.
[38]Ronzaud C., Loffing-Cueni D., Hausel P., et al. Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension [J]. The Journal of clinical investigation,2013,123(2):657-665.
[39]Ellison D. H. Ubiquitylation and the pathogenesis of hypertension [J]. The Journal of clinical investigation,2013,123(2):546-548.
[40]Van Huysse J. W., Amin M. S., Yang B., et al. Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain [J]. Hypertension,2012,60(3):691-696.
[41]Botero-Velez M., Curtis J. J., Warnock D. G. Brief report:Liddle's syndrome revisited--a disorder of sodium reabsorption in the distal tubule [J]. The New England journal of medicine,1994,330(3):178-181.
[42]Hughey R. P., Bruns J. B., Kinlough C. L., et al. Epithelial sodium channels are activated by furin-dependent proteolysis [J]. The Journal of biological chemistry,2004, 279(18):18111-18114.
[43]Dahlmann A., Pradervand S., Hummler E., et al. Mineralocorticoid regulation of epithelial Na+ channels is maintained in a mouse model of Liddle's syndrome [J]. American journal of physiology Renal physiology,2003,285(2):F310-318.
[44]Debonneville C., Flores S. Y., Kamynina E., et al. Phosphorylation of Nedd4-2 by Sgkl regulates epithelial Na(+) channel cell surface expression [J]. EMBO J,2001, 20(24):7052-7059.
[45]Snyder P. M., Olson D. R., Kabra R., et al. cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4-2 [J]. The Journal of biological chemistry,2004, 279(44):45753-45758.
[46]Snyder P. M., Olson D. R., Thomas B. C. Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+channel [J]. The Journal of biological chemistry,2002,277(1):5-8.
[47]Blazer-Yost B. L., Liu X., Helman S. I. Hormonal regulation of ENaCs:insulin and aldosterone [J]. The American journal of physiology,1998,274(5 Pt 1):C1373-1379.
[48]Bubien J. K. Epithelial Na+ channel (ENaC), hormones, and hypertension [J]. The Journal of biological chemistry,2010,285(31):23527-23531.
[49]Fakitsas P., Adam G, Daidie D., et al. Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation [J]. Journal of the American Society of Nephrology:JASN,2007,18(4):1084-1092.
[50]Whelton P. K. Urinary sodium and cardiovascular disease risk:informing guidelines for sodium consumption [J]. JAMA,2011,306(20):2262-2264.
[51]Ruffieux-Daidie D., Poirot O., Boulkroun S., et al. Deubiquitylation regulates activation and proteolytic cleavage of ENaC [J]. Journal of the American Society of Nephrology:JASN,2008,19(11):2170-2180.
[52]Butterworth M. B., Edinger R. S., Ovaa H., et al. The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel [J]. The Journal of biological chemistry,2007,282(52):37885-37893.
[53]Zhou R., Tomkovicz V. R., Butler P. L., et al. Ubiquitin-specific peptidase 8 (USP8) regulates endosomal trafficking of the epithelial Na+ channel [J]. The Journal of biological chemistry,2013,288(8):5389-5397.
[54]Pradervand S., Wang Q., Burnier M., et al. A mouse model for Liddle's syndrome [J]. Journal of the American Society of Nephrology:JASN,1999,10(12):2527-2533.
[55]Pradervand S., Vandewalle A., Bens M., et al. Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome [J]. Journal of the American Society of Nephrology:JASN,2003,14(9):2219-2228.
[56]Konstas A. A., Mavrelos D., Korbmacher C. Conservation of pH sensitivity in the epithelial sodium channel (ENaC) with Liddle's syndrome mutation [J]. Pflugers Archiv: European journal of physiology,2000,441(2-3):341-350.
[57]Ambrosius W. T., Bloem L. J., Zhou L., et al. Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension [J]. Hypertension,1999,34(4 Pt 1):631-637.
[58]Sheridan M. B., Fong P., Groman J. D., et al. Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome [J]. Human
[1]Budnitz D. S., Lovegrove M. C., Shehab N., et al. Emergency hospitalizations for adverse drug events in older Americans [J]. The New England journal of medicine,2011, 365(21):2002-2012.
[2]Gage B. F., Eby C., Johnson J. A., et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin [J]. Clinical pharmacology and therapeutics, 2008,84(3):326-331.
[3]Lane S., Al-Zubiedi S., Hatch E., et al. The population pharmacokinetics of R-and S-warfarin:effect of genetic and clinical factors [J]. British journal of clinical pharmacology,2012,73(1):66-76.
[4]Wittkowsky A. K. Warfarin and other coumarin derivatives:pharmacokinetics, pharmacodynamics, and drug interactions [J]. Seminars in vascular medicine,2003,3(3): 221-230.
[5]Kaminsky L. S., Zhang Z. Y. Human P450 metabolism of warfarin [J]. Pharmacology & therapeutics,1997,73(1):67-74.
[6]Takahashi H., Echizen H. Pharmacogenetics of warfarin elimination and its clinical implications [J]. Clinical pharmacokinetics,2001,40(8):587-603.
[7]Cain D., Hutson S. M., Wallin R. Assembly of the warfarin-sensitive vitamin K 2,3-epoxide reductase enzyme complex in the endoplasmic reticulum membrane [J]. The Journal of biological chemistry,1997,272(46):29068-29075.
[8]Schwarz U. I., Ritchie M. D., Bradford Y., et al. Genetic determinants of response to warfarin during initial anticoagulation [J]. The New England journal of medicine,2008, 358(10):999-1008.
[9]Holbrook A., Schulman S., Witt D. M, et al. Evidence-based management of anticoagulant therapy:Antithrombotic Therapy and Prevention of Thrombosis,9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [J]. Chest,2012,141(2 Suppl):e152S-184S.
[10]Takahashi H., Ieiri I., Wilkinson G. R., et al.5'-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients [J]. Blood,2004,103(8):3055-3057.
[11]Zhao F., Loke C., Rankin S. C., et al. Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose [J]. Clinical pharmacology and therapeutics,2004,76(3):210-219.
[12]Yuan H. Y., Chen J. J., Lee M. T., et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity [J]. Human molecular genetics,2005,14(13):1745-1751.
[13]Veenstra D. L., You J. H., Rieder M. J., et al. Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population [J]. Pharmacogenetics and genomics,2005,15(10):687-691.
[14]Tham L. S., Goh B. C., Nafziger A., et al. A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9 [J]. Clinical pharmacology and therapeutics,2006,80(4): 346-355.
[15]Miao L., Yang J., Huang C., et al. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin:proposal for a new dosing regimen in Chinese patients [J]. European journal of clinical pharmacology,2007, 63(12):1135-1141.
[16]Wen M. S., Lee M., Chen J. J., et al. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes [J]. Clinical pharmacology and therapeutics,2008,84(1):83-89.
[17]Huang S. W., Chen H. S., Wang X. Q., et al. Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose:a prospective study in Chinese patients [J]. Pharmacogenetics and genomics,2009,19(3):226-234.
[18]Lee M. T, Chen C. H., Chou C. H., et al. Genetic determinants of warfarin dosing in the Han-Chinese population [J]. Pharmacogenomics,2009,10(12):1905-1913.
[19]Lenzini P., Wadelius M., Kimmel S., et al. Integration of genetic, clinical, and INR data to refine warfarin dosing [J]. Clinical pharmacology and therapeutics,2010,87(5): 572-578.
[20]Cooper G. M., Johnson J. A., Langaee T. Y., et al. A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose [J]. Blood,2008, 112(4):1022-1027.
[21]Choi J. R., Kim J. O., Kang D. R., et al. Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients [J]. Journal of human genetics,2011,56(4): 290-295.
[22]Sconce E. A., Khan T. I., Wynne H. A., et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen [J]. Blood,2005,106(7):2329-2333.
[23]Johnson J. A., Gong L., Whirl-Carrillo M., et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing [J]. Clinical pharmacology and therapeutics,2011,90(4):625-629.
[24]Sagreiya H., Berube C., Wen A., et al. Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9 [J]. Pharmacogenetics and genomics,2010,20(7):407-413.
[25]Gong I. Y., Schwarz U. I., Crown N., et al. Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation [J]. PloS one,2011,6(11):e27808.
[26]Caldwell M. D., Awad T., Johnson J. A., et al. CYP4F2 genetic variant alters required warfarin dose [J]. Blood,2008,111(8):4106-4112.
[27]Wei M., Ye F., Xie D., et al. A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and VKORC1 and clinical variables:derivation in Han Chinese patients with non valvular atrial fibrillation [J]. Thrombosis and haemostasis,2012,107(6):1083-1091.
[28]Zhong S. L., Yu X. Y., Liu Y., et al. Integrating interacting drugs and genetic variations to improve the predictability of warfarin maintenance dose in Chinese patients [J]. Pharmacogenetics and genomics,2012,22(3):176-182.
[29]Rusdiana T., Araki T., Nakamura T., et al. Responsiveness to low-dose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population [J]. European journal of clinical pharmacology,2013,69(3): 395-405.
[30]Cha P. C., Mushiroda T., Takahashi A., et al. High-resolution SNP and haplotype maps of the human gamma-glutamyl carboxylase gene (GGCX) and association study between polymorphisms in GGCX and the warfarin maintenance dose requirement of the Japanese population [J]. Journal of human genetics,2007,52(10):856-864.
[31]Chan S. L., Goh B. C., Chia K. S., et al. Effects of CYP4F2 and GGCX genetic variants on maintenance warfarin dose in a multi-ethnic Asian population [J]. Thrombosis and haemostasis,2011,105(6):1100-1102.
[32]Huang S. W., Xiang D. K., Huang L., et al. Influence of GGCX genotype on warfarin dose requirements in Chinese patients [J]. Thrombosis research,2011,127(2): 131-134.
[33]Luxembourg B., Schneider K., Sittinger K., et al. Impact of pharmacokinetic (CYP2C9) and pharmacodynamic (VKORC1, F7, GGCX, CALU, EPHX1) gene variants on the initiation and maintenance phases of phenprocoumon therapy [J]. Thrombosis and haemostasis,2011,105(1):169-180.
[34]Wang T. L., Li H. L., Tjong W. Y., et al. Genetic factors contribute to patient-specific warfarin dose for Han Chinese [J]. Clinica chimica acta; international journal of clinical chemistry,2008,396(1-2):76-79.
[35]Pautas E., Moreau C., Gouin-Thibault I., et al. Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients [J]. Clinical pharmacology and therapeutics,2010,87(1):57-64.
[36]Gu Q., Kong Y, Schneede J., et al. VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China [J]. European journal of clinical pharmacology,2010,66(12):1217-1227.
[37]Voora D., Koboldt D. C., King C. R., et al. A polymorphism in the VKORC1 regulator calumenin predicts higher warfarin dose requirements in African Americans [J]. Clinical pharmacology and therapeutics,2010,87(4):445-451.
[38]Liu H., Zhao Y., Nie D., et al. Association of a functional cytochrome P450 4F2 haplotype with urinary 20-HETE and hypertension [J]. Journal of the American Society of Nephrology:JASN,2008,19(4):714-721.
[39]Costea I., Mack D. R., Israel D., et al. Genes involved in the metabolism of poly-unsaturated fatty-acids (PUFA) and risk for Crohn's disease in children & young adults [J]. PloS one,2010,5(12):e15672.
[40]You J. H., Wong R. S., Waye M. M., et al. Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients [J]. Journal of thrombosis and thrombolysis,2011,31(1):113-118.
[41]Tan S. L., Li Z., Song G. B., et al. Development and comparison of a new personalized warfarin stable dose prediction algorithm in Chinese patients undergoing heart valve replacement [J]. Die Pharmazie,2012,67(11):930-937.
[42]Lei X., Guo Y., Sun J., et al. Accuracy assessment of pharmaco genetic algorithms for warfarin dose prediction in Chinese patients [J]. American journal of hematology,2012, 87(5):541-544.
[43]Dong L., Shi Y. K., Tian Z. P., et al. [Low intensity anticoagulation therapy after mechanical heart valve replacement] [J]. Zhonghua wai ke za zhi [Chinese journal of surgery],2003,41(4):250-252.
[44]Haibo Z., Jinzhong L., Yan L., et al. Low-intensity international normalized ratio (INR) oral anticoagulant therapy in Chinese patients with mechanical heart valve prostheses [J]. Cell biochemistry and biophysics,2012,62(1):147-151.
[45]Wu J., Wang J., Jiang S., et al. The efficacy and safety of low intensity warfarin therapy in Chinese elderly atrial fibrillation patients with high CHADS2 risk score [J]. International journal of cardiology,2013,167(6):3067-3068.
[46]You J. H., Chan F. W., Wong R. S., et al. Is INR between 2.0 and 3.0 the optimal level for Chinese patients on warfarin therapy for moderate-intensity anticoagulation? [J]. British journal of clinical pharmacology,2005,59(5):582-587.
[47]Zhou X. M., Zhuang W., Hu J. G, et al. Low-dose anticoagulation in Chinese patients with mechanical heart valves [J]. Asian cardiovascular & thoracic annals,2005, 13(4):341-344.
[48]Wang Y, Zhang W., Zhang Y., et al. VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection) [J]. Circulation, 2006,113(12):1615-1621.
[49]Chern H. D., Ueng T. H., Fu Y P., et al. CYP2C9 polymorphism and warfarin sensitivity in Taiwan Chinese [J]. Clinica chimica acta; international journal of clinical chemistry,2006,367(1-2):108-113.
[50]Suriapranata I. M., Tjong W. Y, Wang T., et al. Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians [J]. BMC medical genetics,2011, 12(80.
[51]Liu Y, Zhong S. L., Tan H. H., et al. [Impact of CYP2C9 and VKORC1 polymorphism on warfarin response during initiation of therapy] [J]. Zhonghua xin xue guan bing za zhi,2011,39(10):929-935.
[52]Mcdonald M. G, Rieder M. J., Nakano M., et al. CYP4F2 is a vitamin Kl oxidase: An explanation for altered warfarin dose in carriers of the V433M variant [J]. Molecular pharmacology,2009,75(6):1337-1346.
[53]Takeuchi F., Mcginnis R., Bourgeois S., et al. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose [J]. PLoS genetics,2009,5(3):e1000433.
[54]Lam M. P., Cheung B. M. The pharmacogenetics of the response to warfarin in Chinese [J]. British journal of clinical pharmacology,2012,73(3):340-347.
[55]Imperatore G, Cadwell B. L., Geiss L., et al. Thirty-year trends in cardiovascular risk factor levels among US adults with diabetes:National Health and Nutrition Examination Surveys,1971-2000 [J]. American journal of epidemiology,2004,160(6): 531-539.
[56]Aso Y, Matsumoto S., Fujiwara Y, et al. Impaired fibrinolytic compensation for hypercoagulability in obese patients with type 2 diabetes:association with increased plasminogen activator inhibitor-1 [J]. Metabolism:clinical and experimental,2002,51(4): 471-476.
[57]Knobl P., Schernthaner G., Schnack C., et al. Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients [J]. Diabetologia,1993,36(10):1045-1050.
[58]Vinik A. I., Erbas T., Park T. S., et al. Platelet dysfunction in type 2 diabetes [J]. Diabetes care,2001,24(8):1476-1485.
[59]Yazbek N., Bapat A., Kleiman N. Platelet abnormalities in diabetes mellitus [J]. Coronary artery disease,2003,14(5):365-371.
[60]Kamali F., Edwards C., Butler T. J., et al. The influence of (R)-and (S)-warfarin, vitamin K and vitamin K epoxide upon warfarin anticoagulation [J]. Thrombosis and haemostasis,2000,84(1):39-42.
[61]Hillman M. A., Wilke R. A., Caldwell M. D., et al. Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype [J]. Pharmacogenetics,2004,14(8): 539-547.
[62]Garcia D., Regan S., Crowther M., et al. Warfarin maintenance dosing patterns in clinical practice:implications for safer anticoagulation in the elderly population [J]. Chest,2005,127(6):2049-2056.
[63]Anderson J. L., Home B. D., Stevens S. M., et al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation [J]. Circulation,2007,116(22):2563-2570.
[64]Caraco Y., Blotnick S., Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation:a prospective randomized controlled study [J]. Clinical pharmacology and therapeutics,2008,83(3):460-470.
[65]Burmester J. K., Berg R. L., Yale S. H., et al. A randomized controlled trial of genotype-based Coumadin initiation [J]. Genetics in medicine:official journal of the American College of Medical Genetics,2011,13(6):509-518.
[66]Pirmohamed M., Burnside G., Eriksson N., et al. A randomized trial of genotype-guided dosing of warfarin [J]. The New England journal of medicine,2013, 369(24):2294-2303.
[67]Kimmel S. E., French B., Kasner S. E., et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing [J]. The New England journal of medicine,2013,369(24): 2283-2293.
[68]Zineh I., Pacanowski M., Woodcock J. Pharmacogenetics and coumarin dosing--recalibrating expectations [J]. The New England journal of medicine,2013, 369(24):2273-2275.
[69]Gao L., He L., Luo J., et al. Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A [J]. Chinese medical journal,2011,124(17): 2767-2770.
[70]Roth J. A., Boudreau D., Fujii M. M., et al. Genetic Risk Factors for Major Bleeding in Warfarin Patients in a Community Setting [J]. Clinical pharmacology and therapeutics, 2014,
[71]Wang M., Lang X., Cui S., et al. Clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality after rheumatic valve replacement:a randomized and controlled trial [J]. International journal of medical sciences,2012,9(6):472-479.
[1]Stranger B. E., Forrest M. S., Dunning M., et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes [J]. Science,2007,315(5813): 848-853.
[2]Bick D., Dimmock D. Whole exome and whole genome sequencing [J]. Current opinion in pediatrics,2011,23(6):594-600.
[3]Majewski J., Schwartzentruber J., Lalonde E., et al. What can exome sequencing do for you? [J]. Journal of medical genetics,2011,48(9):580-589.
[4]Chan L., Boerwinkle E. Gene-Environment Interactions and Gene Therapy in Atherosclerosis [J]. Cardiology in Review,1994,2(3):130-137.
[5]Roberts R. A customized genetic approach to the number one killer:coronary artery disease [J]. Current opinion in cardiology,2008,23(6):629-633.
[6]Dang M. T., Hambleton J., Kayser S. R. The influence of ethnicity on warfarin dosage requirement [J]. The Annals of pharmacotherapy,2005,39(6):1008-1012.
[7]Roberts R., Stewart A. F., Wells G. A., et al. Identifying genes for coronary artery disease:An idea whose time has come [J]. The Canadian journal of cardiology,2007,23 Suppl A(7A-15A.
[8]Mcpherson R., Pertsemlidis A., Kavaslar N., et al. A common allele on chromosome 9 associated with coronary heart disease [J]. Science,2007,316(5830):1488-1491.
[9]Helgadottir A., Thorleifsson G, Manolescu A., et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction [J]. Science,2007,316(5830): 1491-1493.
[10]Preuss M., Konig I. R., Thompson J. R., et al. Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study:A Genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls [J]. Circulation Cardiovascular genetics,2010,3(5):475-483.
[11]Roberts R., Stewart A. F. Genes and coronary artery disease:where are we? [J]. Journal of the American College of Cardiology,2012,60(18):1715-1721.
[12]Manolio T. A., Collins F. S., Cox N. J., et al. Finding the missing heritability of complex diseases [J]. Nature,2009,461(7265):747-753.
[13]Kearney P. M., Whelton M., Reynolds K., et al. Global burden of hypertension: analysis of worldwide data [J]. Lancet,2005,365(9455):217-223.
[14]Perkovic V., Huxley R., Wu Y., et al. The burden of blood pressure-related disease:a neglected priority for global health [J]. Hypertension,2007,50(6):991-997.
[15]Lewington S., Clarke R., Qizilbash N., et al. Age-specific relevance of usual blood pressure to vascular mortality:a meta-analysis of individual data for one million adults in 61 prospective studies [J]. Lancet,2002,360(9349):1903-1913.
[16]Feinleib M., Garrison R. J., Fabsitz R., et al. The NHLBI twin study of cardiovascular disease risk factors:methodology and summary of results [J]. American journal of epidemiology,1977,106(4):284-285.
[17]Mongeau J. G., Biron P., Sing C. F. The influence of genetics and household environment upon the variability of normal blood pressure:the Montreal Adoption Survey [J]. Clinical and experimental hypertension Part A, Theory and practice,1986, 8(4-5):653-660.
[18]Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J]. Nature,2007,447(7145):661-678.
[19]Ehret G. B., Munroe P. B., Rice K. M., et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk [J]. Nature,2011,478(7367): 103-109.
[20]Newton-Cheh C., Johnson T., Gateva V., et al. Genome-wide association study identifies eight loci associated with blood pressure [J]. Nature genetics,2009,41(6): 666-676.
[21]Levy D., Ehret G. B., Rice K., et al. Genome-wide association study of blood pressure and hypertension [J]. Nature genetics,2009,41(6):677-687.
[22]Kato N., Takeuchi F., Tabara Y., et al. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians [J]. Nature genetics,2011,43(6):531-538.
[23]Wain L. V, Verwoert G. C., O'reilly P. F., et al. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure [J]. Nature genetics,2011,43(10):1005-1011.
[24]Ehret G B., Caulfield M. J. Genes for blood pressure:an opportunity to understand hypertension [J]. European heart journal,2013,34(13):951-961.
[25]Keating B. J., Tischfield S., Murray S. S., et al. Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies [J]. PloS one,2008,3(10):e3583.
[26]Johnson T., Gaunt T. R., Newhouse S. J., et al. Blood pressure loci identified with a gene-centric array [J]. American journal of human genetics,2011,89(6):688-700.
[27]Tomaszewski M., Debiec R., Braund P. S., et al. Genetic architecture of ambulatory blood pressure in the general population:insights from cardiovascular gene-centric array [J]. Hypertension,2010,56(6):1069-1076.
[28]Dickstein K., Cohen-Solal A., Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008:the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) [J]. European heart journal,2008,29(19):2388-2442.
[29]Mcmurray J. J., Adamopoulos S., Anker S. D., et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012:The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC [J]. European heart journal,2012,33(14):1787-1847.
[30]Cowie M. R., Fox K. F., Wood D. A., et al. Hospitalization of patients with heart failure:a population-based study [J]. European heart journal,2002,23(11):877-885.
[31]Loehr L. R., Rosamond W. D., Chang P. P., et al. Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study) [J]. The American journal of cardiology,2008,101(7):1016-1022.
[32]Lee D. S., Pencina M. J., Benjamin E. J., et al. Association of parental heart failure with risk of heart failure in offspring [J]. The New England journal of medicine,2006, 355(2):138-147.
[33]Packer M. The neurohormonal hypothesis:a theory to explain the mechanism of disease progression in heart failure [J]. Journal of the American College of Cardiology, 1992,20(1):248-254.
[34]Dorn G. W.,2nd. Adrenergic signaling polymorphisms and their impact on cardiovascular disease [J]. Physiological reviews,2010,90(3):1013-1062.
[35]Abecasis G. R., Altshuler D., Auton A., et al. A map of human genome variation from population-scale sequencing [J]. Nature,2010,467(7319):1061-1073.
[36]Mason D. A., Moore J. D., Green S. A., et al. A gain-of-function polymorphism in a G-protein coupling domain of the human betal-adrenergic receptor [J]. The Journal of biological chemistry,1999,274(18):12670-12674.
[37]Joseph S. S., Lynham J. A., Grace A. A., et al. Markedly reduced effects of (-)-isoprenaline but not of (-)-CGP12177 and unchanged affinity of beta-blockers at Gly389-betal-adrenoceptors compared to Arg389-betal-adrenoceptors [J]. British journal of pharmacology,2004,142(1):51-56.
[38]Rathz D. A., Gregory K. N., Fang Y., et al. Hierarchy of polymorphic variation and desensitization permutations relative to beta 1-and beta 2-adrenergic receptor signaling [J]. The Journal of biological chemistry,2003,278(12):10784-10789. [39]Rochais F., Vilardaga J. P., Nikolaev V. O., et al. Real-time optical recording of betal-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to
carvedilol [J]. The Journal of clinical investigation,2007,117(1):229-235. [40] Wagoner L. E., Craft L. L., Zengel P., et al. Polymorphisms of the betal-adrenergic receptor predict exercise capacity in heart failure [J]. American heart journal,2002, 144(5):840-846.
[41]Sandilands A. J., Parameshwar J., Large S., et al. Confirmation of a role for the 389R>G beta-1 adrenoceptor polymorphism on exercise capacity in heart failure [J]. Heart,2005,91(12):1613-1614.
[42]Terra S. G, Hamilton K. K., Pauly D. F., et al. Betal-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy [J]. Pharmacogenetics and genomics,2005,15(4):227-234.
[43]Terra S. G, Pauly D. F., Lee C. R., et al. beta-Adrenergic receptor polymorphisms and responses during titration of metoprolol controlled release/extended release in heart failure [J]. Clinical pharmacology and therapeutics,2005,77(3):127-137.
[44]Chen L., Meyers D., Javorsky G, et al. Arg389Gly-betal-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol [J]. Pharmacogenetics and genomics,2007,17(11):941-949.
[45]Petersen M., Andersen J. T., Hjelvang B. R., et al. Association of beta-adrenergic receptor polymorphisms and mortality in carvedilol-treated chronic heart-failure patients [J]. British journal of clinical pharmacology,2011,71(4):556-565.
[46]Rigat B., Hubert C., Alhenc-Gelas F., et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels [J]. The Journal of clinical investigation,1990,86(4):1343-1346.
[47]Danser A. H., Schalekamp M. A., Bax W. A., et al. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism [J]. Circulation,1995, 92(6):1387-1388.
[48]Lechin M., Quinones M. A., Omran A., et al. Angiotensin-I converting enzyme genotypes and left ventricular hypertrophy in patients with hypertrophic cardiomyopathy [J]. Circulation,1995,92(7):1808-1812.
[49]Mcnamara D. M., Holubkov R., Postava L., et al. Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure [J]. Journal of the American College of Cardiology,2004,44(10):2019-2026.
[50]Li X., Li Y., Jia N., et al. Angiotensin-converting enzyme gene deletion allele increases the risk of left ventricular hypertrophy:evidence from a meta-analysis [J]. Molecular biology reports,2012,39(12):10063-10075.
[51]Bai Y., Wang L., Hu S., et al. Association of angiotensin-converting enzyme I/D polymorphism with heart failure:a meta-analysis [J]. Molecular and cellular biochemistry,2012,361(1-2):297-304.
[52]Smith N. L., Felix J. F., Morrison A. C., et al. Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry:a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium [J]. Circulation Cardiovascular genetics,2010, 3(3):256-266.
[53]Morrison A. C., Felix J. F., Cupples L. A., et al. Genomic variation associated with mortality among adults of European and African ancestry with heart failure:the cohorts for heart and aging research in genomic epidemiology consortium [J]. Circulation Cardiovascular genetics,2010,3(3):248-255.
[54]Cappola T. P., Li M., He J., et al. Common variants in HSPB7 and FRMD4B associated with advanced heart failure [J]. Circulation Cardiovascular genetics,2010, 3(2):147-154.
[55]Stark K., Esslinger U. B., Reinhard W., et al. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy [J]. PLoS genetics,2010, 6(10):e1001167.
[56]Cappola T. P., Matkovich S. J., Wang W., et al. Loss-of-function DNA sequence variant in the CLCNKA chloride channel implicates the cardio-renal axis in interindividual heart failure risk variation [J]. Proceedings of the National Academy of Sciences of the United States of America,2011,108(6):2456-2461.
[57]Lomvardas S., Barnea G., Pisapia D. J., et al. Interchromosomal interactions and olfactory receptor choice [J]. Cell,2006,126(2):403-413.
[58]Sotelo J., Esposito D., Duhagon M. A., et al. Long-range enhancers on 8q24 regulate c-Myc [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(7):3001-3005.
[59]Marian A. J. Challenges in medical applications of whole exome/genome sequencing discoveries [J]. Trends in cardiovascular medicine,2012,22(8):219-223.
[60]Herman D. S., Lam L., Taylor M. R., et al. Truncations of titin causing dilated cardiomyopathy [J]. The New England journal of medicine,2012,366(7):619-628.
[61]Bolton J. L., Stewart M. C., Wilson J. F., et al. Improvement in prediction of coronary heart disease risk over conventional risk factors using SNPs identified in genome-wide association studies [J]. PloS one,2013,8(2):e57310.
[62]Hughes M. F., Saarela O., Stritzke J., et al. Genetic markers enhance coronary risk prediction in men:the MORGAM prospective cohorts [J]. PloS one,2012,7(7):e40922.
[63]Davies R. W., Dandona S., Stewart A. F., et al. Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies [J]. Circulation Cardiovascular genetics,2010, 3(5):468-474.
[64]Qi L., Ma J., Qi Q., et al. Genetic risk score and risk of myocardial infarction in Hispanics [J]. Circulation,2011,123(4):374-380.
[65]Sayols-Baixeras S., Lluis-Ganella C., Lucas G, et al. Pathogenesis of coronary artery disease:focus on genetic risk factors and identification of genetic variants [J]. The application of clinical genetics,2014,7(15-32.
[66]Goldstein J. L., Brown M. S. The LDL receptor [J]. Arteriosclerosis, thrombosis, and vascular biology,2009,29(4):431-438.
[67]Lifton R. P., Gharavi A. G, Geller D. S. Molecular mechanisms of human hypertension [J]. Cell,2001,104(4):545-556. [68]Mansfield T. A., Simon D. B., Farfel Z., et al. Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type Ⅱ, to chromosomes
1q31-42 and 17p11-q21 [J]. Nature genetics,1997,16(2):202-205. [69]Wilson F. H., Disse-Nicodeme S., Choate K. A., et al. Human hypertension caused by mutations in WNK kinases [J]. Science,2001,293(5532):1107-1112.
[70]Boyden L. M., Choi M., Choate K. A., et al. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities [J]. Nature,2012,482(7383):98-102.
[71]Louis-Dit-Picard H., Bare J., Trujillano D., et al. K.LHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron [J]. Nature genetics,2012,44(4):456-460, S451-453.
[72]Newhouse S., Farrall M., Wallace C, et al. Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion [J]. PloS one, 2009,4(4):e5003.
[73]Newhouse S. J., Wallace C., Dobson R., et al. Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British Genetics of Hypertension study [J]. Human molecular genetics,2005,14(13): 1805-1814.
[74]Tobin M. D., Raleigh S. M., Newhouse S., et al. Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population [J]. Circulation,2005,112(22):3423-3429.
[75]Tobin M. D., Timpson N. J., Wain L. V., et al. Common variation in the WNK1 gene and blood pressure in childhood:the Avon Longitudinal Study of Parents and Children [J]. Hypertension,2008,52(5):974-979.
[76]Tobin M. D., Tomaszewski M., Braund P. S., et al. Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population [J]. Hypertension,2008,51(6):1658-1664.
[77]Ji W., Foo J. N., O'roak B. J., et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation [J]. Nature genetics,2008,40(5):592-599.
[78]Elliott P., Andersson B., Arbustini E., et al. Classification of the cardiomyopathies:a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases [J]. European heart journal,2008,29(2):270-276.
[79]Jacoby D., Mckenna W. J. Genetics of inherited cardiomyopathy [J]. European heart journal,2012,33(3):296-304.
[80]Geisterfer-Lowrance A. A., Kass S., Tanigawa G., et al. A molecular basis for familial hypertrophic cardiomyopathy:a beta cardiac myosin heavy chain gene missense mutation [J]. Cell,1990,62(5):999-1006.
[81]Lim D. S., Oberst L., Mccluggage M., et al. Decreased left ventricular ejection fraction in transgenic mice expressing mutant cardiac troponin T-Q(92), responsible for human hypertrophic cardiomyopathy [J]. Journal of molecular and cellular cardiology, 2000,32(3):365-374.
[82]Marian A. J., Wu Y., Lim D. S., et al. A transgenic rabbit model for human hypertrophic cardiomyopathy [J]. The Journal of clinical investigation,1999,104(12): 1683-1692.
[83]Kimura A., Harada H., Park J. E., et al. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy [J]. Nature genetics,1997,16(4):379-382.
[84]Keren A., Syrris P., Mckenna W. J. Hypertrophic cardiomyopathy:the genetic determinants of clinical disease expression [J]. Nature clinical practice Cardiovascular medicine,2008,5(3):158-168.
[85]31opes L. R., Elliott P. M. Genetics of heart failure [J]. Biochimica et biophysica acta, 2013,1832(12):2451-2461.
[86]Gavazzi A., Repetto A., Scelsi L., et al. Evidence-based diagnosis of familial non-X-linked dilated cardiomyopathy. Prevalence, inheritance and characteristics [J]. European heart journal,2001,22(1):73-81.
[87]Hershberger R. E., Siegfried J. D. Update 2011:clinical and genetic issues in familial dilated cardiomyopathy [J]. Journal of the American College of Cardiology,2011, 57(16):1641-1649.
[88]Van Rijsingen I. A., Arbustini E., Elliott P. M., et al. Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study [J]. Journal of the American College of Cardiology,2012,59(5):493-500.
[89]Van Berlo J. H., De Voogt W. G, Van Der Kooi A. J., et al. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations:do lamin A/C mutations portend a high risk of sudden death? [J]. J Mol Med (Berl),2005,83(1):79-83.
[90]Theis J. L., Sharpe K. M., Matsumoto M. E., et al. Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal recessive dilated cardiomyopathy [J]. Circulation Cardiovascular genetics,2011,4(6):585-594.
[91]Klaassen S., Probst S., Oechslin E., et al. Mutations in sarcomere protein genes in left ventricular noncompaction [J]. Circulation,2008,117(22):2893-2901.
[92]Hoedemaekers Y. M., Caliskan K., Michels M., et al. The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy [J]. Circulation Cardiovascular genetics,2010,3(3): 232-239.
[93]Mckoy G., Protonotarios N., Crosby A., et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease) [J]. Lancet,2000,355(9221):2119-2124.
[94]Azaouagh A., Churzidse S., Konorza T., et al. Arrhythmogenic right ventricular cardiomyopathy/dysplasia:a review and update [J]. Clin Res Cardiol,2011,100(5): 383-394.
[95]Watkins H., Ashrafian H., Redwood C. Inherited cardiomyopathies [J]. The New England journal of medicine,2011,364(17):1643-1656.
[96]Kaski J. P., Syrris P., Burch M., et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes [J]. Heart,2008, 94(11):1478-1484.
[97]Van Spaendonck-Zwarts K. Y., Van Hessem L., Jongbloed J. D., et al. Desmin-related myopathy [J]. Clinical genetics,2011,80(4):354-366.
[98]lroberts R., Marian A. J., Dandona S., et al. Genomics in cardiovascular disease [J]. Journal of the American College of Cardiology,2013,61(20):2029-2037.
[99]Charron P., Arad M., Arbustini E., et al. Genetic counselling and testing in cardiomyopathies:a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases [J]. European heart journal,2010,31(22): 2715-2726.
[100]Pennisi E. Search for Pore-fection [J]. Science,2012,336(6081):534-537.
[101]Kazui M., Nishiya Y., Ishizuka T., et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite [J]. Drug metabolism and disposition:the biological fate of chemicals,2010,38(1):92-99.
[102]Sangkuhl K., Klein T. E., Altman R. B. Clopidogrel pathway [J]. Pharmacogenetics and genomics,2010,20(7):463-465.
[103]De Morais S. M., Wilkinson G. R., Blaisdell J., et al. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans [J]. The Journal of biological chemistry,1994,269(22):15419-15422.
[104]Scott S. A., Sangkuhl K., Shuldiner A. R., et al. PharmGKB summary:very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19 [J]. Pharmacogenetics and genomics,2012,22(2):159-165.
[105]Li-Wan-Po A., Girard T., Farndon P., et al. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17 [J]. British journal of clinical pharmacology,2010,69(3):222-230.
[106]Brandt J. T., Close S. L., Iturria S. J.,, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel [J]. Journal of thrombosis and haemostasis:JTH,2007, 5(12):2429-2436.
[107]Kim K. A., Park P. W., Hong S. J., et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel:a possible mechanism for clopidogrel resistance [J]. Clinical pharmacology and therapeutics,2008,84(2): 236-242.
[108]Hulot J. S., Bura A., Villard E., et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects [J]. Blood,2006,108(7):2244-2247.
[109]Shuldiner A. R., O'connell J. R., Bliden K. P., et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy [J]. JAMA:the journal of the American Medical Association,2009,302(8): 849-857.
[110]Wallentin L., James S., Storey R. F., et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes:a genetic substudy of the PLATO trial [J]. Lancet,2010,376(9749):1320-1328.
[111]Mega J. L., Close S. L., Wiviott S. D., et al. Cytochrome p-450 polymorphisms and response to clopidogrel [J]. The New England journal of medicine,2009,360(4): 354-362.
[112]Simon T., Verstuyft C., Mary-Krause M., et al. Genetic determinants of response to clopidogrel and cardiovascular events [J]. The New England journal of medicine,2009, 360(4):363-375.
[113]Sibbing D., Stegherr J., Latz W., et al. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention [J]. European heart journal,2009,30(8):916-922.
[114]6johnson J. A., Cavallari L. H. Pharmacogenetics and cardiovascular disease--implications for personalized medicine [J]. Pharmacological reviews,2013, 65(3):987-1009.
[115]Yusuf S., Zhao F., Mehta S. R., et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation [J]. The New England journal of medicine,2001,345(7):494-502.
[116]Connolly S. J., Pogue J., Hart R. G., et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation [J]. The New England journal of medicine,2009, 360(20):2066-2078.
[117]Mega J. L., Simon T., Collet J. P., et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI:a meta-analysis [J]. JAMA:the journal of the American Medical Association,2010,304(16):1821-1830.
[118]Harmsze A. M., Van Werkum J. W., Hackeng C. M., et al. The influence of CYP2C19*2 and *17 on on-treatment platelet reactivity and bleeding events in patients undergoing elective coronary stenting [J]. Pharmacogenetics and genomics,2012,22(3): 169-175.
[119]Mega J. L., Hochholzer W., Frelinger A. L.,3rd, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease [J]. JAMA:the journal of the American Medical Association, 2011,306(20):2221-2228.
[120]Roberts J. D., Wells G. A., Le May M. R., et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE):a prospective, randomised, proof-of-concept trial [J]. Lancet,2012,379(9827):1705-1711.
[121]Anderson J. L., Adams C. D., Antman E. M., et al.2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [J]. Circulation,2011,123(18):e426-579.
[122]Levine G. N., Bates E. R., Blankenship J. C., et al.2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions [J]. Circulation,2011, 124(23):e574-651.
[123]Wright R. S., Anderson J. L., Adams C. D., et al.2011 ACCF/AHA focused update of the Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction (updating the 2007 guideline):a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons [J]. Journal of the American College of Cardiology,2011, 57(19):1920-1959.
[124]Budnitz D. S., Lovegrove M. C., Shehab N., et al. Emergency hospitalizations for adverse drug events in older Americans [J]. The New England journal of medicine, 2011,365(21):2002-2012.
[125]Lenzini P., Wadelius M., Kimmel S., et al. Integration of genetic, clinical, and INR data to refine warfarin dosing [J]. Clinical pharmacology and therapeutics,2010, 87(5):572-578.
[126]Takeuchi F., Mcginnis R., Bourgeois S., et al. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose [J]. PLoS genetics,2009,5(3):e1000433.
[127]Scordo M. G., Pengo V., Spina E., et al. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance [J]. Clinical pharmacology and therapeutics,2002,72(6):702-710.
[128]Rost S., Fregin A., Ivaskevicius V., et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2 [J]. Nature,2004,427(6974): 537-541.
[129]Aquilante C. L., Langaee T. Y., Lopez L. M., et al. Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements [J]. Clinical pharmacology and therapeutics,2006,79(4):291-302.
[130]Cavallari L. H., Langaee T. Y, Momary K. M., et al. Genetic and clinical predictors of warfarin dose requirements in African Americans [J]. Clinical pharmacology and therapeutics,2010,87(4):459-464.
[131]Limdi N. A., Wadelius M., Cavallari L., et al. Warfarin pharmacogenetics:a single VKORC1 polymorphism is predictive of dose across 3 racial groups [J]. Blood, 2010,115(18):3827-3834.
[132]Carlquist J. F., Anderson J. L. Using pharmacogenetics in real time to guide warfarin initiation:a clinician update [J]. Circulation,2011,124(23):2554-2559.
[133]Anderson J. L., Home B. D., Stevens S. M., et al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation [J]. Circulation,2007,116(22):2563-2570.
[134]Caraco Y, Blotnick S., Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation:a prospective randomized controlled study [J]. Clinical pharmacology and therapeutics,2008,83(3): 460-470.
[135]Burmester J. K., Berg R. L., Yale S. H., et al. A randomized controlled trial of genotype-based Coumadin initiation [J]. Genetics in medicine:official journal of the American College of Medical Genetics,2011,13(6):509-518.
[136]Pirmohamed M., Burnside G, Eriksson N., et al. A randomized trial of genotype-guided dosing of warfarin [J]. The New England journal of medicine,2013, 369(24):2294-2303.
[137]Kimmel S. E., French B., Kasner S. E., et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing [J]. The New England journal of medicine,2013, 369(24):2283-2293.
[138]Zineh I., Pacanowski M., Woodcock J. Pharmacogenetics and coumarin dosing--recalibrating expectations [J]. The New England journal of medicine,2013, 369(24):2273-2275.
[139]Gao L., He L., Luo J., et al. Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A [J]. Chinese medical journal,2011, 124(17):2767-2770.
[140]Roth J. A., Boudreau D., Fujii M. M., et al. Genetic Risk Factors for Major Bleeding in Warfarin Patients in a Community Setting [J]. Clinical pharmacology and therapeutics,2014,
[141]Wang M., Lang X., Cui S., et al. Clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality after rheumatic valve replacement:a randomized and controlled trial [J]. International journal of medical sciences,2012,9(6):472-479.
[142]Bruckert E., Hayem G, Dejager S., et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study [J]. Cardiovascular drugs and therapy/sponsored by the International Society of Cardiovascular Pharmacotherapy,2005,19(6):403-414.
[143]Link E., Parish S., Armitage J., et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study [J]. The New England journal of medicine,2008,359(8): 789-799.
[144]Pasanen M. K., Fredrikson H., Neuvonen P. J., et al. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin [J]. Clinical pharmacology and therapeutics,2007,82(6):726-733.
[145]Brunham L. R., Lansberg P. J., Zhang L., et al. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin [J]. The pharmacogenomics journal,2012,12(3):233-237.
[146]Wilke R. A., Ramsey L. B., Johnson S. G., et al. The clinical pharmacogenomics implementation consortium:CPIC guideline for SLCO1B1 and simvastatin-induced myopathy [J]. Clinical pharmacology and therapeutics,2012,92(1):112-117.
[147]Iakoubova O. A., Tong C. H., Rowland C. M., et al. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials:the CARE and WOSCOPS trials [J]. Journal of the American College of Cardiology,2008,51(4):435-443.
[148]Iakoubova O. A., Robertson M., Tong C. H., et al. KIF6 Trp719Arg polymorphism and the effect of statin therapy in elderly patients:results from the PROSPER study [J]. European journal of cardiovascular prevention and rehabilitation official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology,2010, 17(4):455-461.
[149]Ference B. A., Yoo W., Flack J. M., et al. A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol:two meta-analyses and a meta-regression analysis [J]. PloS one,2011,6(12):e28834.
[150]Chasman D. I., Giulianini F., Macfadyen J., et al. Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction:the Justification for the Use of Statins in Prevention:an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial [J]. Circulation Cardiovascular genetics,2012,5(2):257-264.
[151]Trompet S., De Craen A. J., Postmus I., et al. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses [J]. BMC medical genetics,2011,12(131.
[152]Hopewell J. C., Parish S., Offer A., et al. Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study [J]. European heart journal,2013,34(13):982-992.
[153]Shiffman D., Trompet S., Louie J. Z., et al. Genome-wide study of gene variants associated with differential cardiovascular event reduction by pravastatin therapy [J]. PloS one,2012,7(5):e38240.
[154]Chan S. W., Hu M., Tomlinson B. The pharmacogenetics of beta-adrenergic receptor antagonists in the treatment of hypertension and heart failure [J]. Expert opinion on drug metabolism & toxicology,2012,8(7):767-790.
[155]O'connor C. M., Fiuzat M., Carson P. E., et al. Combinatorial pharmacogenetic interactions of bucindolol and betal, alpha2C adrenergic receptor polymorphisms [J]. PloS one,2012,7(10):e44324.
[156]Vandell A. G., Lobmeyer M. T., Gawronski B. E., et al. G protein receptor kinase 4 polymorphisms:beta-blocker pharmacogenetics and treatment-related outcomes in hypertension [J]. Hypertension,2012,60(4):957-964.
[157]Lobmeyer M. T., Gong Y., Terra S. G, et al. Synergistic polymorphisms of betal and alpha2C-adrenergic receptors and the influence on left ventricular ejection fraction response to beta-blocker therapy in heart failure [J]. Pharmacogenetics and genomics, 2007,17(4):277-282.
[158]Schwartz G. L., Turner S. T. Pharmacogenetics of antihypertensive drug responses [J]. American journal of pharmacogenomics:genomics-related research in drug development and clinical practice,2004,4(3):151-160.
[159]Johnson J. A. Advancing management of hypertension through pharmacogenomics [J]. Annals of medicine,2012,44 Suppl 1 (S17-22.
[160]Arnett D. K., Claas S. A. Pharmacogenetics of antihypertensive treatment: detailing disciplinary dissonance [J]. Pharmacogenomics,2009,10(8):1295-1307.
[161]Turner S. T., Bailey K. R., Fridley B. L., et al. Genomic association analysis suggests chromosome 12 locus influencing antihypertensive response to thiazide diuretic [J]. Hypertension,2008,52(2):359-365.
[162]Duarte J. D., Turner S. T., Tran B., et al. Association of chromosome 12 locus with antihypertensive response to hydrochlorothiazide may involve differential YEATS4 expression [J]. The pharmacogenomics journal,2013,13(3):257-263.
[163]Gong Y., Mcdonough C. W., Wang Z., et al. Hypertension susceptibility loci and blood pressure response to antihypertensives:results from the pharmacogenomic evaluation of antihypertensive responses study [J]. Circulation Cardiovascular genetics, 2012,5(6):686-691.
[164]Lifton R. P., Dluhy R. G, Powers M., et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension [J]. Nature,1992,355(6357):262-265.
[165]Hansson J. H., Nelson-Williams C., Suzuki H., et al. Hypertension caused by a truncated epithelial sodium channel gamma subunit:genetic heterogeneity of Liddle syndrome [J]. Nature genetics,1995,11(1):76-82.
[2]Feinleib M., Garrison R. J., Fabsitz R., et al. The NHLBI twin study of cardiovascular disease risk factors:methodology and summary of results [J]. American journal of epidemiology,1977,106(4):284-285.
[3]Mongeau J. G, Biron P., Sing C. F. The influence of genetics and household environment upon the variability of normal blood pressure:the Montreal Adoption Survey [J]. Clinical and experimental hypertension Part A, Theory and practice,1986, 8(4-5):653-660.
[4]Manolio T. A., Collins F. S., Cox N. J., et al. Finding the missing heritability of complex diseases [J]. Nature,2009,461(7265):747-753.
[5]Newton-Cheh C., Johnson T., Gateva V., et al. Genome-wide association study identifies eight loci associated with blood pressure [J]. Nature genetics,2009,41(6): 666-676.
[6]Levy D., Ehret G. B., Rice K., et al. Genome-wide association study of blood pressure and hypertension [J]. Nature genetics,2009,41(6):677-687.
[7]Kato N., Takeuchi F., Tabara Y., et al. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians [J]. Nature genetics,2011,43(6):531-538.
[8]Ehret G. B., Munroe P. B., Rice K. M., et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk [J]. Nature,2011,478(7367): 103-109.
[9]Wain L. V., Verwoert G. C., O'reilly P. F., et al. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure [J]. Nature genetics,2011,43(10):1005-1011.
[10]Liddle G. W., Bledsoe T., Coppage W. S. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. [J]. Trans Assoc Am Physicians 1963,76(199-213.
[11]Takahashi H., Ieiri I., Wilkinson G. R., et al.5'-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients [J]. Blood,2004,103(8):3055-3057.
[12]Zhao F., Loke C., Rankin S. C., et al. Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose [J]. Clinical pharmacology and therapeutics,2004,76(3):210-219.
[13]Yuan H. Y., Chen J. J., Lee M. T., et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity [J]. Human molecular genetics,2005,14(13):1745-1751.
[14]Veenstra D. L., You J. H., Rieder M. J., et al. Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population [J]. Pharmacogenetics and genomics,2005,15(10):687-691.
[15]Tham L. S., Goh B. C., Nafziger A., et al. A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9 [J]. Clinical pharmacology and therapeutics,2006,80(4): 346-355.
[16]Miao L., Yang J., Huang C., et al. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin:proposal for a new dosing regimen in Chinese patients [J]. European journal of clinical pharmacology,2007, 63(12):1135-1141.
[17]Wen M. S., Lee M., Chen J. J., et al. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes [J]. Clinical pharmacology and therapeutics,2008,84(1):83-89.
[18]Huang S. W., Chen H. S., Wang X. Q., et al. Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose:a prospective study in Chinese patients [J]. Pharmacogenetics and genomics,2009,19(3):226-234.
[19]Lee M. T., Chen C. H., Chou C. H., et al. Genetic determinants of warfarin dosing in the Han-Chinese population [J]. Pharmacogenomics,2009,10(12):1905-1913.
[20]Lenzini P., Wadelius M., Kimmel S., et al. Integration of genetic, clinical, and INR data to refine warfarin dosing [J]. Clinical pharmacology and therapeutics,2010,87(5): 572-578.
[21]Sagreiya H., Berube C., Wen A., et al. Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9 [J]. Pharmacogenetics and genomics,2010,20(7):407-413.
[22]Gong I. Y., Schwarz U. I., Crown N., et al. Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation [J]. PloS one,2011,6(11):e27808.
[23]Caldwell M. D., Awad T., Johnson J. A., et al. CYP4F2 genetic variant alters required warfarin dose [J]. Blood,2008,111(8):4106-4112.
[24]Wei M., Ye F., Xie D., et al. A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and VKORC1 and clinical variables:derivation in Han Chinese patients with non valvular atrial fibrillation [J]. Thrombosis and haemostasis,2012,107(6):1083-1091.
[25]You J. H., Wong R. S., Waye M. M., et al. Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients [J]. Journal of thrombosis and thrombolysis,2011,31(1):113-118.
[26]Zhong S. L., Yu X. Y, Liu Y, et al. Integrating interacting drugs and genetic variations to improve the predictability of warfarin maintenance dose in Chinese patients [J]. Pharmacogenetics and genomics,2012,22(3):176-182.
[27]Tan S. L., Li Z., Song G. B., et al. Development and comparison of a new personalized warfarin stable dose prediction algorithm in Chinese patients undergoing heart valve replacement [J]. Die Pharmazie,2012,67(11):930-937.
[1]Liddle G. W., Bledsoe T., Coppage W. S. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. [J]. Trans Assoc Am Physicians 1963,76(199-213).
[2]Firsov D., Schild L., Gautschi I., et al. Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome:a quantitative approach [J]. Proceedings of the National Academy of Sciences of the United States of America,1996,93(26): 15370-15375.
[3]Hansson J. H., Schild L., Lu Y., et al. A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity [J]. Proceedings of the National Academy of Sciences of the United States of America,1995, 92(25):11495-11499.
[4]Canessa C. M., Schild L., Buell G, et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits [J]. Nature,1994,367(6462):463-467.
[5]Hiltunen T. P., Hannila-Handelberg T., Petajaniemi N., et al. Liddle's syndrome associated with a point mutation in the extracellular domain of the epithelial sodium channel gamma subunit [J]. J Hypertens,2002,20(12):2383-2390.
[6]Rayner B. L., Owen E. P., King J. A., et al. A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension [J]. Journal of hypertension,2003,21(5):921-926.
[7]Snyder P. M., Price M. P., Mcdonald F. J., et al. Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel [J]. Cell,1995, 83(6):969-978.
[8]Schild L., Lu Y., Gautschi I., et al. Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome [J]. The EMBO journal,1996,15(10):2381-2387.
[9]World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects [J]. JAMA,1997,277(11): 925-926.
[10]Shi J. Y., Chen X., Ren Y., et al. [Liddle's syndrome caused by a novel mutation of the gamma-subunit of epithelial sodium channel gene SCNN1G in Chinese] [J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2010,27(2):132-135.
[11]Shimkets R. A., Warnock D. G, Bositis C. M., et al. Liddle's syndrome:heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel [J]. Cell,1994,79(3):407-414.
[12]Kyuma M., Ura N., Torii T., et al. A family with liddle's syndrome caused by a mutation in the beta subunit of the epithelial sodium channel [J]. Clin Exp Hypertens, 2001,23(6):471-478.
[13]Melander O., Orho M., Fagerudd J., et al. Mutations and variants of the epithelial sodium channel gene in Liddle's syndrome and primary hypertension [J]. Hypertension, 1998,31(5):1118-1124.
[14]Inoue T., Okauchi Y, Matsuzaki Y, et al. Identification of a single cytosine base insertion mutation at Arg-597 of the beta subunit of the human epithelial sodium channel in a family with Liddle's disease [J]. Eur J Endocrinol,1998,138(6):691-697.
[15]Jackson S. N., Williams B., Houtman P., et al. The diagnosis of Liddle syndrome by identification of a mutation in the beta subunit of the epithelial sodium channel [J]. Journal of medical genetics,1998,35(6):510-512.
[16]Nakano Y, Ishida T., Ozono R., et al. A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome [J]. Journal of hypertension,2002,20(12):2379-2382.
[17]Jeunemaitre X., Bassilana F., Persu A., et al. Genotype-phenotype analysis of a newly discovered family with Liddle's syndrome [J]. J Hypertens,1997,15(10): 1091-1100.
[18]Hansson J. H., Nelson-Williams C., Suzuki H., et al. Hypertension caused by a truncated epithelial sodium channel gamma subunit:genetic heterogeneity of Liddle syndrome [J]. Nature genetics,1995,11(1):76-82.
[19]Wang W., Zhou W., Jiang L., et al. Mutation analysis of SCNN1B in a family with Liddle's syndrome [J]. Endocrine,2006,29(3):385-390.
[20]Inoue J., Iwaoka T., Tokunaga H., et al. A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel [J]. J Clin Endocrinol Metab,1998,83(6):2210-2213.
[21]Gao P. J., Zhang K. X., Zhu D. L., et al. Diagnosis of Liddle syndrome by genetic analysis of beta and gamma subunits of epithelial sodium channel--a report of five affected family members [J]. Journal of hypertension,2001,19(5):885-889.
[22]Yamashita Y., Koga M., Takeda Y., et al. Two sporadic cases of Liddle's syndrome caused by De novo ENaC mutations [J]. Am J Kidney Dis,2001,37(3):499-504.
[23]Uehara Y, Sasaguri M., Kinoshita A., et al. Genetic analysis of the epithelial sodium channel in Liddle's syndrome [J]. J Hypertens,1998,16(8):1131-1135.
[24]Freundlich M., Ludwig M. A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome [J]. Pediatr Nephrol,2005,20(4): 512-515.
[25]Tamura H., Schild L., Enomoto N., et al. Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene [J]. The Journal of clinical investigation,1996,97(7):1780-1784.
[26]Rossi E., Farnetti E., Debonneville A., et al. Liddle's syndrome caused by a novel missense mutation (P617L) of the epithelial sodium channel beta subunit [J]. J Hypertens, 2008,26(5):921-927.
[27]Sawathiparnich P., Sumboonnanonda A., Weerakulwattana P., et al. A novel mutation in the beta-subunit of the epithelial sodium channel gene (SCNN1B) in a Thai family with Liddle's syndrome [J]. J Pediatr Endocrinol Metab,2009,22(1):85-89.
[28]Gao L., Wang L., Liu Y, et al. A family with Liddle syndrome caused by a novel missense mutation in the PY motif of the beta-subunit of the epithelial sodium channel [J]. The Journal of pediatrics,2013,162(1):166-170.
[29]Wang Y., Zheng Y., Chen J., et al. A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome [J]. Clinical endocrinology,2007, 67(5):801-804.
[30]Jones E. S., Owen E. P., Davidson J. S., et al. The R563Q mutation of the epithelial sodium channel beta-subunit is associated with hypertension [J]. Cardiovascular journal of Africa,2011,22(5):241-244.
[31]Rossi E., Farnetti E., Nicoli D., et al. A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome [J]. American journal of hypertension,2011,24(8):930-935.
[32]Bertog M., Cuffe J. E., Pradervand S., et al. Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome [J]. The Journal of physiology,2008,586(2):459-475.
[33]Bogdanovic R., Kuburovic V., Stajic N., et al. Liddle syndrome in a Serbian family and literature review of underlying mutations [J]. European journal of pediatrics,2012, 171(3):471-478.
[34]Wang L. P., Gao L. G, Zhou X. L., et al. Genetic diagnosis of Liddle's syndrome by mutation analysis of SCNNIB and SCNNIG in a Chinese family [J]. Chinese medical journal,2012,125(8):1401-1404.
[35]Staub O., Gautschi I., Ishikawa T., et al. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination [J]. The EMBO journal,1997,16(21): 6325-6336.
[36]Lu C., Pribanic S., Debonneville A., et al. The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool [J]. Traffic,2007,8(9):1246-1264.
[37]Araki N., Umemura M., Miyagi Y., et al. Expression, transcription, and possible antagonistic interaction of the human Nedd4L gene variant:implications for essential hypertension [J]. Hypertension,2008,51(3):773-777.
[38]Ronzaud C., Loffing-Cueni D., Hausel P., et al. Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension [J]. The Journal of clinical investigation,2013,123(2):657-665.
[39]Ellison D. H. Ubiquitylation and the pathogenesis of hypertension [J]. The Journal of clinical investigation,2013,123(2):546-548.
[40]Van Huysse J. W., Amin M. S., Yang B., et al. Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain [J]. Hypertension,2012,60(3):691-696.
[41]Botero-Velez M., Curtis J. J., Warnock D. G. Brief report:Liddle's syndrome revisited--a disorder of sodium reabsorption in the distal tubule [J]. The New England journal of medicine,1994,330(3):178-181.
[42]Hughey R. P., Bruns J. B., Kinlough C. L., et al. Epithelial sodium channels are activated by furin-dependent proteolysis [J]. The Journal of biological chemistry,2004, 279(18):18111-18114.
[43]Dahlmann A., Pradervand S., Hummler E., et al. Mineralocorticoid regulation of epithelial Na+ channels is maintained in a mouse model of Liddle's syndrome [J]. American journal of physiology Renal physiology,2003,285(2):F310-318.
[44]Debonneville C., Flores S. Y., Kamynina E., et al. Phosphorylation of Nedd4-2 by Sgkl regulates epithelial Na(+) channel cell surface expression [J]. EMBO J,2001, 20(24):7052-7059.
[45]Snyder P. M., Olson D. R., Kabra R., et al. cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4-2 [J]. The Journal of biological chemistry,2004, 279(44):45753-45758.
[46]Snyder P. M., Olson D. R., Thomas B. C. Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+channel [J]. The Journal of biological chemistry,2002,277(1):5-8.
[47]Blazer-Yost B. L., Liu X., Helman S. I. Hormonal regulation of ENaCs:insulin and aldosterone [J]. The American journal of physiology,1998,274(5 Pt 1):C1373-1379.
[48]Bubien J. K. Epithelial Na+ channel (ENaC), hormones, and hypertension [J]. The Journal of biological chemistry,2010,285(31):23527-23531.
[49]Fakitsas P., Adam G, Daidie D., et al. Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation [J]. Journal of the American Society of Nephrology:JASN,2007,18(4):1084-1092.
[50]Whelton P. K. Urinary sodium and cardiovascular disease risk:informing guidelines for sodium consumption [J]. JAMA,2011,306(20):2262-2264.
[51]Ruffieux-Daidie D., Poirot O., Boulkroun S., et al. Deubiquitylation regulates activation and proteolytic cleavage of ENaC [J]. Journal of the American Society of Nephrology:JASN,2008,19(11):2170-2180.
[52]Butterworth M. B., Edinger R. S., Ovaa H., et al. The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel [J]. The Journal of biological chemistry,2007,282(52):37885-37893.
[53]Zhou R., Tomkovicz V. R., Butler P. L., et al. Ubiquitin-specific peptidase 8 (USP8) regulates endosomal trafficking of the epithelial Na+ channel [J]. The Journal of biological chemistry,2013,288(8):5389-5397.
[54]Pradervand S., Wang Q., Burnier M., et al. A mouse model for Liddle's syndrome [J]. Journal of the American Society of Nephrology:JASN,1999,10(12):2527-2533.
[55]Pradervand S., Vandewalle A., Bens M., et al. Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome [J]. Journal of the American Society of Nephrology:JASN,2003,14(9):2219-2228.
[56]Konstas A. A., Mavrelos D., Korbmacher C. Conservation of pH sensitivity in the epithelial sodium channel (ENaC) with Liddle's syndrome mutation [J]. Pflugers Archiv: European journal of physiology,2000,441(2-3):341-350.
[57]Ambrosius W. T., Bloem L. J., Zhou L., et al. Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension [J]. Hypertension,1999,34(4 Pt 1):631-637.
[58]Sheridan M. B., Fong P., Groman J. D., et al. Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome [J]. Human
[1]Budnitz D. S., Lovegrove M. C., Shehab N., et al. Emergency hospitalizations for adverse drug events in older Americans [J]. The New England journal of medicine,2011, 365(21):2002-2012.
[2]Gage B. F., Eby C., Johnson J. A., et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin [J]. Clinical pharmacology and therapeutics, 2008,84(3):326-331.
[3]Lane S., Al-Zubiedi S., Hatch E., et al. The population pharmacokinetics of R-and S-warfarin:effect of genetic and clinical factors [J]. British journal of clinical pharmacology,2012,73(1):66-76.
[4]Wittkowsky A. K. Warfarin and other coumarin derivatives:pharmacokinetics, pharmacodynamics, and drug interactions [J]. Seminars in vascular medicine,2003,3(3): 221-230.
[5]Kaminsky L. S., Zhang Z. Y. Human P450 metabolism of warfarin [J]. Pharmacology & therapeutics,1997,73(1):67-74.
[6]Takahashi H., Echizen H. Pharmacogenetics of warfarin elimination and its clinical implications [J]. Clinical pharmacokinetics,2001,40(8):587-603.
[7]Cain D., Hutson S. M., Wallin R. Assembly of the warfarin-sensitive vitamin K 2,3-epoxide reductase enzyme complex in the endoplasmic reticulum membrane [J]. The Journal of biological chemistry,1997,272(46):29068-29075.
[8]Schwarz U. I., Ritchie M. D., Bradford Y., et al. Genetic determinants of response to warfarin during initial anticoagulation [J]. The New England journal of medicine,2008, 358(10):999-1008.
[9]Holbrook A., Schulman S., Witt D. M, et al. Evidence-based management of anticoagulant therapy:Antithrombotic Therapy and Prevention of Thrombosis,9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [J]. Chest,2012,141(2 Suppl):e152S-184S.
[10]Takahashi H., Ieiri I., Wilkinson G. R., et al.5'-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients [J]. Blood,2004,103(8):3055-3057.
[11]Zhao F., Loke C., Rankin S. C., et al. Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose [J]. Clinical pharmacology and therapeutics,2004,76(3):210-219.
[12]Yuan H. Y., Chen J. J., Lee M. T., et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity [J]. Human molecular genetics,2005,14(13):1745-1751.
[13]Veenstra D. L., You J. H., Rieder M. J., et al. Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population [J]. Pharmacogenetics and genomics,2005,15(10):687-691.
[14]Tham L. S., Goh B. C., Nafziger A., et al. A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9 [J]. Clinical pharmacology and therapeutics,2006,80(4): 346-355.
[15]Miao L., Yang J., Huang C., et al. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin:proposal for a new dosing regimen in Chinese patients [J]. European journal of clinical pharmacology,2007, 63(12):1135-1141.
[16]Wen M. S., Lee M., Chen J. J., et al. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes [J]. Clinical pharmacology and therapeutics,2008,84(1):83-89.
[17]Huang S. W., Chen H. S., Wang X. Q., et al. Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose:a prospective study in Chinese patients [J]. Pharmacogenetics and genomics,2009,19(3):226-234.
[18]Lee M. T, Chen C. H., Chou C. H., et al. Genetic determinants of warfarin dosing in the Han-Chinese population [J]. Pharmacogenomics,2009,10(12):1905-1913.
[19]Lenzini P., Wadelius M., Kimmel S., et al. Integration of genetic, clinical, and INR data to refine warfarin dosing [J]. Clinical pharmacology and therapeutics,2010,87(5): 572-578.
[20]Cooper G. M., Johnson J. A., Langaee T. Y., et al. A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose [J]. Blood,2008, 112(4):1022-1027.
[21]Choi J. R., Kim J. O., Kang D. R., et al. Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients [J]. Journal of human genetics,2011,56(4): 290-295.
[22]Sconce E. A., Khan T. I., Wynne H. A., et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen [J]. Blood,2005,106(7):2329-2333.
[23]Johnson J. A., Gong L., Whirl-Carrillo M., et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing [J]. Clinical pharmacology and therapeutics,2011,90(4):625-629.
[24]Sagreiya H., Berube C., Wen A., et al. Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9 [J]. Pharmacogenetics and genomics,2010,20(7):407-413.
[25]Gong I. Y., Schwarz U. I., Crown N., et al. Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation [J]. PloS one,2011,6(11):e27808.
[26]Caldwell M. D., Awad T., Johnson J. A., et al. CYP4F2 genetic variant alters required warfarin dose [J]. Blood,2008,111(8):4106-4112.
[27]Wei M., Ye F., Xie D., et al. A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and VKORC1 and clinical variables:derivation in Han Chinese patients with non valvular atrial fibrillation [J]. Thrombosis and haemostasis,2012,107(6):1083-1091.
[28]Zhong S. L., Yu X. Y., Liu Y., et al. Integrating interacting drugs and genetic variations to improve the predictability of warfarin maintenance dose in Chinese patients [J]. Pharmacogenetics and genomics,2012,22(3):176-182.
[29]Rusdiana T., Araki T., Nakamura T., et al. Responsiveness to low-dose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population [J]. European journal of clinical pharmacology,2013,69(3): 395-405.
[30]Cha P. C., Mushiroda T., Takahashi A., et al. High-resolution SNP and haplotype maps of the human gamma-glutamyl carboxylase gene (GGCX) and association study between polymorphisms in GGCX and the warfarin maintenance dose requirement of the Japanese population [J]. Journal of human genetics,2007,52(10):856-864.
[31]Chan S. L., Goh B. C., Chia K. S., et al. Effects of CYP4F2 and GGCX genetic variants on maintenance warfarin dose in a multi-ethnic Asian population [J]. Thrombosis and haemostasis,2011,105(6):1100-1102.
[32]Huang S. W., Xiang D. K., Huang L., et al. Influence of GGCX genotype on warfarin dose requirements in Chinese patients [J]. Thrombosis research,2011,127(2): 131-134.
[33]Luxembourg B., Schneider K., Sittinger K., et al. Impact of pharmacokinetic (CYP2C9) and pharmacodynamic (VKORC1, F7, GGCX, CALU, EPHX1) gene variants on the initiation and maintenance phases of phenprocoumon therapy [J]. Thrombosis and haemostasis,2011,105(1):169-180.
[34]Wang T. L., Li H. L., Tjong W. Y., et al. Genetic factors contribute to patient-specific warfarin dose for Han Chinese [J]. Clinica chimica acta; international journal of clinical chemistry,2008,396(1-2):76-79.
[35]Pautas E., Moreau C., Gouin-Thibault I., et al. Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients [J]. Clinical pharmacology and therapeutics,2010,87(1):57-64.
[36]Gu Q., Kong Y, Schneede J., et al. VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China [J]. European journal of clinical pharmacology,2010,66(12):1217-1227.
[37]Voora D., Koboldt D. C., King C. R., et al. A polymorphism in the VKORC1 regulator calumenin predicts higher warfarin dose requirements in African Americans [J]. Clinical pharmacology and therapeutics,2010,87(4):445-451.
[38]Liu H., Zhao Y., Nie D., et al. Association of a functional cytochrome P450 4F2 haplotype with urinary 20-HETE and hypertension [J]. Journal of the American Society of Nephrology:JASN,2008,19(4):714-721.
[39]Costea I., Mack D. R., Israel D., et al. Genes involved in the metabolism of poly-unsaturated fatty-acids (PUFA) and risk for Crohn's disease in children & young adults [J]. PloS one,2010,5(12):e15672.
[40]You J. H., Wong R. S., Waye M. M., et al. Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients [J]. Journal of thrombosis and thrombolysis,2011,31(1):113-118.
[41]Tan S. L., Li Z., Song G. B., et al. Development and comparison of a new personalized warfarin stable dose prediction algorithm in Chinese patients undergoing heart valve replacement [J]. Die Pharmazie,2012,67(11):930-937.
[42]Lei X., Guo Y., Sun J., et al. Accuracy assessment of pharmaco genetic algorithms for warfarin dose prediction in Chinese patients [J]. American journal of hematology,2012, 87(5):541-544.
[43]Dong L., Shi Y. K., Tian Z. P., et al. [Low intensity anticoagulation therapy after mechanical heart valve replacement] [J]. Zhonghua wai ke za zhi [Chinese journal of surgery],2003,41(4):250-252.
[44]Haibo Z., Jinzhong L., Yan L., et al. Low-intensity international normalized ratio (INR) oral anticoagulant therapy in Chinese patients with mechanical heart valve prostheses [J]. Cell biochemistry and biophysics,2012,62(1):147-151.
[45]Wu J., Wang J., Jiang S., et al. The efficacy and safety of low intensity warfarin therapy in Chinese elderly atrial fibrillation patients with high CHADS2 risk score [J]. International journal of cardiology,2013,167(6):3067-3068.
[46]You J. H., Chan F. W., Wong R. S., et al. Is INR between 2.0 and 3.0 the optimal level for Chinese patients on warfarin therapy for moderate-intensity anticoagulation? [J]. British journal of clinical pharmacology,2005,59(5):582-587.
[47]Zhou X. M., Zhuang W., Hu J. G, et al. Low-dose anticoagulation in Chinese patients with mechanical heart valves [J]. Asian cardiovascular & thoracic annals,2005, 13(4):341-344.
[48]Wang Y, Zhang W., Zhang Y., et al. VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection) [J]. Circulation, 2006,113(12):1615-1621.
[49]Chern H. D., Ueng T. H., Fu Y P., et al. CYP2C9 polymorphism and warfarin sensitivity in Taiwan Chinese [J]. Clinica chimica acta; international journal of clinical chemistry,2006,367(1-2):108-113.
[50]Suriapranata I. M., Tjong W. Y, Wang T., et al. Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians [J]. BMC medical genetics,2011, 12(80.
[51]Liu Y, Zhong S. L., Tan H. H., et al. [Impact of CYP2C9 and VKORC1 polymorphism on warfarin response during initiation of therapy] [J]. Zhonghua xin xue guan bing za zhi,2011,39(10):929-935.
[52]Mcdonald M. G, Rieder M. J., Nakano M., et al. CYP4F2 is a vitamin Kl oxidase: An explanation for altered warfarin dose in carriers of the V433M variant [J]. Molecular pharmacology,2009,75(6):1337-1346.
[53]Takeuchi F., Mcginnis R., Bourgeois S., et al. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose [J]. PLoS genetics,2009,5(3):e1000433.
[54]Lam M. P., Cheung B. M. The pharmacogenetics of the response to warfarin in Chinese [J]. British journal of clinical pharmacology,2012,73(3):340-347.
[55]Imperatore G, Cadwell B. L., Geiss L., et al. Thirty-year trends in cardiovascular risk factor levels among US adults with diabetes:National Health and Nutrition Examination Surveys,1971-2000 [J]. American journal of epidemiology,2004,160(6): 531-539.
[56]Aso Y, Matsumoto S., Fujiwara Y, et al. Impaired fibrinolytic compensation for hypercoagulability in obese patients with type 2 diabetes:association with increased plasminogen activator inhibitor-1 [J]. Metabolism:clinical and experimental,2002,51(4): 471-476.
[57]Knobl P., Schernthaner G., Schnack C., et al. Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients [J]. Diabetologia,1993,36(10):1045-1050.
[58]Vinik A. I., Erbas T., Park T. S., et al. Platelet dysfunction in type 2 diabetes [J]. Diabetes care,2001,24(8):1476-1485.
[59]Yazbek N., Bapat A., Kleiman N. Platelet abnormalities in diabetes mellitus [J]. Coronary artery disease,2003,14(5):365-371.
[60]Kamali F., Edwards C., Butler T. J., et al. The influence of (R)-and (S)-warfarin, vitamin K and vitamin K epoxide upon warfarin anticoagulation [J]. Thrombosis and haemostasis,2000,84(1):39-42.
[61]Hillman M. A., Wilke R. A., Caldwell M. D., et al. Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype [J]. Pharmacogenetics,2004,14(8): 539-547.
[62]Garcia D., Regan S., Crowther M., et al. Warfarin maintenance dosing patterns in clinical practice:implications for safer anticoagulation in the elderly population [J]. Chest,2005,127(6):2049-2056.
[63]Anderson J. L., Home B. D., Stevens S. M., et al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation [J]. Circulation,2007,116(22):2563-2570.
[64]Caraco Y., Blotnick S., Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation:a prospective randomized controlled study [J]. Clinical pharmacology and therapeutics,2008,83(3):460-470.
[65]Burmester J. K., Berg R. L., Yale S. H., et al. A randomized controlled trial of genotype-based Coumadin initiation [J]. Genetics in medicine:official journal of the American College of Medical Genetics,2011,13(6):509-518.
[66]Pirmohamed M., Burnside G., Eriksson N., et al. A randomized trial of genotype-guided dosing of warfarin [J]. The New England journal of medicine,2013, 369(24):2294-2303.
[67]Kimmel S. E., French B., Kasner S. E., et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing [J]. The New England journal of medicine,2013,369(24): 2283-2293.
[68]Zineh I., Pacanowski M., Woodcock J. Pharmacogenetics and coumarin dosing--recalibrating expectations [J]. The New England journal of medicine,2013, 369(24):2273-2275.
[69]Gao L., He L., Luo J., et al. Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A [J]. Chinese medical journal,2011,124(17): 2767-2770.
[70]Roth J. A., Boudreau D., Fujii M. M., et al. Genetic Risk Factors for Major Bleeding in Warfarin Patients in a Community Setting [J]. Clinical pharmacology and therapeutics, 2014,
[71]Wang M., Lang X., Cui S., et al. Clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality after rheumatic valve replacement:a randomized and controlled trial [J]. International journal of medical sciences,2012,9(6):472-479.
[1]Stranger B. E., Forrest M. S., Dunning M., et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes [J]. Science,2007,315(5813): 848-853.
[2]Bick D., Dimmock D. Whole exome and whole genome sequencing [J]. Current opinion in pediatrics,2011,23(6):594-600.
[3]Majewski J., Schwartzentruber J., Lalonde E., et al. What can exome sequencing do for you? [J]. Journal of medical genetics,2011,48(9):580-589.
[4]Chan L., Boerwinkle E. Gene-Environment Interactions and Gene Therapy in Atherosclerosis [J]. Cardiology in Review,1994,2(3):130-137.
[5]Roberts R. A customized genetic approach to the number one killer:coronary artery disease [J]. Current opinion in cardiology,2008,23(6):629-633.
[6]Dang M. T., Hambleton J., Kayser S. R. The influence of ethnicity on warfarin dosage requirement [J]. The Annals of pharmacotherapy,2005,39(6):1008-1012.
[7]Roberts R., Stewart A. F., Wells G. A., et al. Identifying genes for coronary artery disease:An idea whose time has come [J]. The Canadian journal of cardiology,2007,23 Suppl A(7A-15A.
[8]Mcpherson R., Pertsemlidis A., Kavaslar N., et al. A common allele on chromosome 9 associated with coronary heart disease [J]. Science,2007,316(5830):1488-1491.
[9]Helgadottir A., Thorleifsson G, Manolescu A., et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction [J]. Science,2007,316(5830): 1491-1493.
[10]Preuss M., Konig I. R., Thompson J. R., et al. Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study:A Genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls [J]. Circulation Cardiovascular genetics,2010,3(5):475-483.
[11]Roberts R., Stewart A. F. Genes and coronary artery disease:where are we? [J]. Journal of the American College of Cardiology,2012,60(18):1715-1721.
[12]Manolio T. A., Collins F. S., Cox N. J., et al. Finding the missing heritability of complex diseases [J]. Nature,2009,461(7265):747-753.
[13]Kearney P. M., Whelton M., Reynolds K., et al. Global burden of hypertension: analysis of worldwide data [J]. Lancet,2005,365(9455):217-223.
[14]Perkovic V., Huxley R., Wu Y., et al. The burden of blood pressure-related disease:a neglected priority for global health [J]. Hypertension,2007,50(6):991-997.
[15]Lewington S., Clarke R., Qizilbash N., et al. Age-specific relevance of usual blood pressure to vascular mortality:a meta-analysis of individual data for one million adults in 61 prospective studies [J]. Lancet,2002,360(9349):1903-1913.
[16]Feinleib M., Garrison R. J., Fabsitz R., et al. The NHLBI twin study of cardiovascular disease risk factors:methodology and summary of results [J]. American journal of epidemiology,1977,106(4):284-285.
[17]Mongeau J. G., Biron P., Sing C. F. The influence of genetics and household environment upon the variability of normal blood pressure:the Montreal Adoption Survey [J]. Clinical and experimental hypertension Part A, Theory and practice,1986, 8(4-5):653-660.
[18]Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J]. Nature,2007,447(7145):661-678.
[19]Ehret G. B., Munroe P. B., Rice K. M., et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk [J]. Nature,2011,478(7367): 103-109.
[20]Newton-Cheh C., Johnson T., Gateva V., et al. Genome-wide association study identifies eight loci associated with blood pressure [J]. Nature genetics,2009,41(6): 666-676.
[21]Levy D., Ehret G. B., Rice K., et al. Genome-wide association study of blood pressure and hypertension [J]. Nature genetics,2009,41(6):677-687.
[22]Kato N., Takeuchi F., Tabara Y., et al. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians [J]. Nature genetics,2011,43(6):531-538.
[23]Wain L. V, Verwoert G. C., O'reilly P. F., et al. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure [J]. Nature genetics,2011,43(10):1005-1011.
[24]Ehret G B., Caulfield M. J. Genes for blood pressure:an opportunity to understand hypertension [J]. European heart journal,2013,34(13):951-961.
[25]Keating B. J., Tischfield S., Murray S. S., et al. Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies [J]. PloS one,2008,3(10):e3583.
[26]Johnson T., Gaunt T. R., Newhouse S. J., et al. Blood pressure loci identified with a gene-centric array [J]. American journal of human genetics,2011,89(6):688-700.
[27]Tomaszewski M., Debiec R., Braund P. S., et al. Genetic architecture of ambulatory blood pressure in the general population:insights from cardiovascular gene-centric array [J]. Hypertension,2010,56(6):1069-1076.
[28]Dickstein K., Cohen-Solal A., Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008:the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) [J]. European heart journal,2008,29(19):2388-2442.
[29]Mcmurray J. J., Adamopoulos S., Anker S. D., et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012:The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC [J]. European heart journal,2012,33(14):1787-1847.
[30]Cowie M. R., Fox K. F., Wood D. A., et al. Hospitalization of patients with heart failure:a population-based study [J]. European heart journal,2002,23(11):877-885.
[31]Loehr L. R., Rosamond W. D., Chang P. P., et al. Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study) [J]. The American journal of cardiology,2008,101(7):1016-1022.
[32]Lee D. S., Pencina M. J., Benjamin E. J., et al. Association of parental heart failure with risk of heart failure in offspring [J]. The New England journal of medicine,2006, 355(2):138-147.
[33]Packer M. The neurohormonal hypothesis:a theory to explain the mechanism of disease progression in heart failure [J]. Journal of the American College of Cardiology, 1992,20(1):248-254.
[34]Dorn G. W.,2nd. Adrenergic signaling polymorphisms and their impact on cardiovascular disease [J]. Physiological reviews,2010,90(3):1013-1062.
[35]Abecasis G. R., Altshuler D., Auton A., et al. A map of human genome variation from population-scale sequencing [J]. Nature,2010,467(7319):1061-1073.
[36]Mason D. A., Moore J. D., Green S. A., et al. A gain-of-function polymorphism in a G-protein coupling domain of the human betal-adrenergic receptor [J]. The Journal of biological chemistry,1999,274(18):12670-12674.
[37]Joseph S. S., Lynham J. A., Grace A. A., et al. Markedly reduced effects of (-)-isoprenaline but not of (-)-CGP12177 and unchanged affinity of beta-blockers at Gly389-betal-adrenoceptors compared to Arg389-betal-adrenoceptors [J]. British journal of pharmacology,2004,142(1):51-56.
[38]Rathz D. A., Gregory K. N., Fang Y., et al. Hierarchy of polymorphic variation and desensitization permutations relative to beta 1-and beta 2-adrenergic receptor signaling [J]. The Journal of biological chemistry,2003,278(12):10784-10789. [39]Rochais F., Vilardaga J. P., Nikolaev V. O., et al. Real-time optical recording of betal-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to
carvedilol [J]. The Journal of clinical investigation,2007,117(1):229-235. [40] Wagoner L. E., Craft L. L., Zengel P., et al. Polymorphisms of the betal-adrenergic receptor predict exercise capacity in heart failure [J]. American heart journal,2002, 144(5):840-846.
[41]Sandilands A. J., Parameshwar J., Large S., et al. Confirmation of a role for the 389R>G beta-1 adrenoceptor polymorphism on exercise capacity in heart failure [J]. Heart,2005,91(12):1613-1614.
[42]Terra S. G, Hamilton K. K., Pauly D. F., et al. Betal-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy [J]. Pharmacogenetics and genomics,2005,15(4):227-234.
[43]Terra S. G, Pauly D. F., Lee C. R., et al. beta-Adrenergic receptor polymorphisms and responses during titration of metoprolol controlled release/extended release in heart failure [J]. Clinical pharmacology and therapeutics,2005,77(3):127-137.
[44]Chen L., Meyers D., Javorsky G, et al. Arg389Gly-betal-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol [J]. Pharmacogenetics and genomics,2007,17(11):941-949.
[45]Petersen M., Andersen J. T., Hjelvang B. R., et al. Association of beta-adrenergic receptor polymorphisms and mortality in carvedilol-treated chronic heart-failure patients [J]. British journal of clinical pharmacology,2011,71(4):556-565.
[46]Rigat B., Hubert C., Alhenc-Gelas F., et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels [J]. The Journal of clinical investigation,1990,86(4):1343-1346.
[47]Danser A. H., Schalekamp M. A., Bax W. A., et al. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism [J]. Circulation,1995, 92(6):1387-1388.
[48]Lechin M., Quinones M. A., Omran A., et al. Angiotensin-I converting enzyme genotypes and left ventricular hypertrophy in patients with hypertrophic cardiomyopathy [J]. Circulation,1995,92(7):1808-1812.
[49]Mcnamara D. M., Holubkov R., Postava L., et al. Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure [J]. Journal of the American College of Cardiology,2004,44(10):2019-2026.
[50]Li X., Li Y., Jia N., et al. Angiotensin-converting enzyme gene deletion allele increases the risk of left ventricular hypertrophy:evidence from a meta-analysis [J]. Molecular biology reports,2012,39(12):10063-10075.
[51]Bai Y., Wang L., Hu S., et al. Association of angiotensin-converting enzyme I/D polymorphism with heart failure:a meta-analysis [J]. Molecular and cellular biochemistry,2012,361(1-2):297-304.
[52]Smith N. L., Felix J. F., Morrison A. C., et al. Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry:a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium [J]. Circulation Cardiovascular genetics,2010, 3(3):256-266.
[53]Morrison A. C., Felix J. F., Cupples L. A., et al. Genomic variation associated with mortality among adults of European and African ancestry with heart failure:the cohorts for heart and aging research in genomic epidemiology consortium [J]. Circulation Cardiovascular genetics,2010,3(3):248-255.
[54]Cappola T. P., Li M., He J., et al. Common variants in HSPB7 and FRMD4B associated with advanced heart failure [J]. Circulation Cardiovascular genetics,2010, 3(2):147-154.
[55]Stark K., Esslinger U. B., Reinhard W., et al. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy [J]. PLoS genetics,2010, 6(10):e1001167.
[56]Cappola T. P., Matkovich S. J., Wang W., et al. Loss-of-function DNA sequence variant in the CLCNKA chloride channel implicates the cardio-renal axis in interindividual heart failure risk variation [J]. Proceedings of the National Academy of Sciences of the United States of America,2011,108(6):2456-2461.
[57]Lomvardas S., Barnea G., Pisapia D. J., et al. Interchromosomal interactions and olfactory receptor choice [J]. Cell,2006,126(2):403-413.
[58]Sotelo J., Esposito D., Duhagon M. A., et al. Long-range enhancers on 8q24 regulate c-Myc [J]. Proceedings of the National Academy of Sciences of the United States of America,2010,107(7):3001-3005.
[59]Marian A. J. Challenges in medical applications of whole exome/genome sequencing discoveries [J]. Trends in cardiovascular medicine,2012,22(8):219-223.
[60]Herman D. S., Lam L., Taylor M. R., et al. Truncations of titin causing dilated cardiomyopathy [J]. The New England journal of medicine,2012,366(7):619-628.
[61]Bolton J. L., Stewart M. C., Wilson J. F., et al. Improvement in prediction of coronary heart disease risk over conventional risk factors using SNPs identified in genome-wide association studies [J]. PloS one,2013,8(2):e57310.
[62]Hughes M. F., Saarela O., Stritzke J., et al. Genetic markers enhance coronary risk prediction in men:the MORGAM prospective cohorts [J]. PloS one,2012,7(7):e40922.
[63]Davies R. W., Dandona S., Stewart A. F., et al. Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies [J]. Circulation Cardiovascular genetics,2010, 3(5):468-474.
[64]Qi L., Ma J., Qi Q., et al. Genetic risk score and risk of myocardial infarction in Hispanics [J]. Circulation,2011,123(4):374-380.
[65]Sayols-Baixeras S., Lluis-Ganella C., Lucas G, et al. Pathogenesis of coronary artery disease:focus on genetic risk factors and identification of genetic variants [J]. The application of clinical genetics,2014,7(15-32.
[66]Goldstein J. L., Brown M. S. The LDL receptor [J]. Arteriosclerosis, thrombosis, and vascular biology,2009,29(4):431-438.
[67]Lifton R. P., Gharavi A. G, Geller D. S. Molecular mechanisms of human hypertension [J]. Cell,2001,104(4):545-556. [68]Mansfield T. A., Simon D. B., Farfel Z., et al. Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type Ⅱ, to chromosomes
1q31-42 and 17p11-q21 [J]. Nature genetics,1997,16(2):202-205. [69]Wilson F. H., Disse-Nicodeme S., Choate K. A., et al. Human hypertension caused by mutations in WNK kinases [J]. Science,2001,293(5532):1107-1112.
[70]Boyden L. M., Choi M., Choate K. A., et al. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities [J]. Nature,2012,482(7383):98-102.
[71]Louis-Dit-Picard H., Bare J., Trujillano D., et al. K.LHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron [J]. Nature genetics,2012,44(4):456-460, S451-453.
[72]Newhouse S., Farrall M., Wallace C, et al. Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion [J]. PloS one, 2009,4(4):e5003.
[73]Newhouse S. J., Wallace C., Dobson R., et al. Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British Genetics of Hypertension study [J]. Human molecular genetics,2005,14(13): 1805-1814.
[74]Tobin M. D., Raleigh S. M., Newhouse S., et al. Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population [J]. Circulation,2005,112(22):3423-3429.
[75]Tobin M. D., Timpson N. J., Wain L. V., et al. Common variation in the WNK1 gene and blood pressure in childhood:the Avon Longitudinal Study of Parents and Children [J]. Hypertension,2008,52(5):974-979.
[76]Tobin M. D., Tomaszewski M., Braund P. S., et al. Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population [J]. Hypertension,2008,51(6):1658-1664.
[77]Ji W., Foo J. N., O'roak B. J., et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation [J]. Nature genetics,2008,40(5):592-599.
[78]Elliott P., Andersson B., Arbustini E., et al. Classification of the cardiomyopathies:a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases [J]. European heart journal,2008,29(2):270-276.
[79]Jacoby D., Mckenna W. J. Genetics of inherited cardiomyopathy [J]. European heart journal,2012,33(3):296-304.
[80]Geisterfer-Lowrance A. A., Kass S., Tanigawa G., et al. A molecular basis for familial hypertrophic cardiomyopathy:a beta cardiac myosin heavy chain gene missense mutation [J]. Cell,1990,62(5):999-1006.
[81]Lim D. S., Oberst L., Mccluggage M., et al. Decreased left ventricular ejection fraction in transgenic mice expressing mutant cardiac troponin T-Q(92), responsible for human hypertrophic cardiomyopathy [J]. Journal of molecular and cellular cardiology, 2000,32(3):365-374.
[82]Marian A. J., Wu Y., Lim D. S., et al. A transgenic rabbit model for human hypertrophic cardiomyopathy [J]. The Journal of clinical investigation,1999,104(12): 1683-1692.
[83]Kimura A., Harada H., Park J. E., et al. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy [J]. Nature genetics,1997,16(4):379-382.
[84]Keren A., Syrris P., Mckenna W. J. Hypertrophic cardiomyopathy:the genetic determinants of clinical disease expression [J]. Nature clinical practice Cardiovascular medicine,2008,5(3):158-168.
[85]31opes L. R., Elliott P. M. Genetics of heart failure [J]. Biochimica et biophysica acta, 2013,1832(12):2451-2461.
[86]Gavazzi A., Repetto A., Scelsi L., et al. Evidence-based diagnosis of familial non-X-linked dilated cardiomyopathy. Prevalence, inheritance and characteristics [J]. European heart journal,2001,22(1):73-81.
[87]Hershberger R. E., Siegfried J. D. Update 2011:clinical and genetic issues in familial dilated cardiomyopathy [J]. Journal of the American College of Cardiology,2011, 57(16):1641-1649.
[88]Van Rijsingen I. A., Arbustini E., Elliott P. M., et al. Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study [J]. Journal of the American College of Cardiology,2012,59(5):493-500.
[89]Van Berlo J. H., De Voogt W. G, Van Der Kooi A. J., et al. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations:do lamin A/C mutations portend a high risk of sudden death? [J]. J Mol Med (Berl),2005,83(1):79-83.
[90]Theis J. L., Sharpe K. M., Matsumoto M. E., et al. Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal recessive dilated cardiomyopathy [J]. Circulation Cardiovascular genetics,2011,4(6):585-594.
[91]Klaassen S., Probst S., Oechslin E., et al. Mutations in sarcomere protein genes in left ventricular noncompaction [J]. Circulation,2008,117(22):2893-2901.
[92]Hoedemaekers Y. M., Caliskan K., Michels M., et al. The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy [J]. Circulation Cardiovascular genetics,2010,3(3): 232-239.
[93]Mckoy G., Protonotarios N., Crosby A., et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease) [J]. Lancet,2000,355(9221):2119-2124.
[94]Azaouagh A., Churzidse S., Konorza T., et al. Arrhythmogenic right ventricular cardiomyopathy/dysplasia:a review and update [J]. Clin Res Cardiol,2011,100(5): 383-394.
[95]Watkins H., Ashrafian H., Redwood C. Inherited cardiomyopathies [J]. The New England journal of medicine,2011,364(17):1643-1656.
[96]Kaski J. P., Syrris P., Burch M., et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes [J]. Heart,2008, 94(11):1478-1484.
[97]Van Spaendonck-Zwarts K. Y., Van Hessem L., Jongbloed J. D., et al. Desmin-related myopathy [J]. Clinical genetics,2011,80(4):354-366.
[98]lroberts R., Marian A. J., Dandona S., et al. Genomics in cardiovascular disease [J]. Journal of the American College of Cardiology,2013,61(20):2029-2037.
[99]Charron P., Arad M., Arbustini E., et al. Genetic counselling and testing in cardiomyopathies:a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases [J]. European heart journal,2010,31(22): 2715-2726.
[100]Pennisi E. Search for Pore-fection [J]. Science,2012,336(6081):534-537.
[101]Kazui M., Nishiya Y., Ishizuka T., et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite [J]. Drug metabolism and disposition:the biological fate of chemicals,2010,38(1):92-99.
[102]Sangkuhl K., Klein T. E., Altman R. B. Clopidogrel pathway [J]. Pharmacogenetics and genomics,2010,20(7):463-465.
[103]De Morais S. M., Wilkinson G. R., Blaisdell J., et al. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans [J]. The Journal of biological chemistry,1994,269(22):15419-15422.
[104]Scott S. A., Sangkuhl K., Shuldiner A. R., et al. PharmGKB summary:very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19 [J]. Pharmacogenetics and genomics,2012,22(2):159-165.
[105]Li-Wan-Po A., Girard T., Farndon P., et al. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17 [J]. British journal of clinical pharmacology,2010,69(3):222-230.
[106]Brandt J. T., Close S. L., Iturria S. J.,, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel [J]. Journal of thrombosis and haemostasis:JTH,2007, 5(12):2429-2436.
[107]Kim K. A., Park P. W., Hong S. J., et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel:a possible mechanism for clopidogrel resistance [J]. Clinical pharmacology and therapeutics,2008,84(2): 236-242.
[108]Hulot J. S., Bura A., Villard E., et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects [J]. Blood,2006,108(7):2244-2247.
[109]Shuldiner A. R., O'connell J. R., Bliden K. P., et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy [J]. JAMA:the journal of the American Medical Association,2009,302(8): 849-857.
[110]Wallentin L., James S., Storey R. F., et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes:a genetic substudy of the PLATO trial [J]. Lancet,2010,376(9749):1320-1328.
[111]Mega J. L., Close S. L., Wiviott S. D., et al. Cytochrome p-450 polymorphisms and response to clopidogrel [J]. The New England journal of medicine,2009,360(4): 354-362.
[112]Simon T., Verstuyft C., Mary-Krause M., et al. Genetic determinants of response to clopidogrel and cardiovascular events [J]. The New England journal of medicine,2009, 360(4):363-375.
[113]Sibbing D., Stegherr J., Latz W., et al. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention [J]. European heart journal,2009,30(8):916-922.
[114]6johnson J. A., Cavallari L. H. Pharmacogenetics and cardiovascular disease--implications for personalized medicine [J]. Pharmacological reviews,2013, 65(3):987-1009.
[115]Yusuf S., Zhao F., Mehta S. R., et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation [J]. The New England journal of medicine,2001,345(7):494-502.
[116]Connolly S. J., Pogue J., Hart R. G., et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation [J]. The New England journal of medicine,2009, 360(20):2066-2078.
[117]Mega J. L., Simon T., Collet J. P., et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI:a meta-analysis [J]. JAMA:the journal of the American Medical Association,2010,304(16):1821-1830.
[118]Harmsze A. M., Van Werkum J. W., Hackeng C. M., et al. The influence of CYP2C19*2 and *17 on on-treatment platelet reactivity and bleeding events in patients undergoing elective coronary stenting [J]. Pharmacogenetics and genomics,2012,22(3): 169-175.
[119]Mega J. L., Hochholzer W., Frelinger A. L.,3rd, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease [J]. JAMA:the journal of the American Medical Association, 2011,306(20):2221-2228.
[120]Roberts J. D., Wells G. A., Le May M. R., et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE):a prospective, randomised, proof-of-concept trial [J]. Lancet,2012,379(9827):1705-1711.
[121]Anderson J. L., Adams C. D., Antman E. M., et al.2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [J]. Circulation,2011,123(18):e426-579.
[122]Levine G. N., Bates E. R., Blankenship J. C., et al.2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions [J]. Circulation,2011, 124(23):e574-651.
[123]Wright R. S., Anderson J. L., Adams C. D., et al.2011 ACCF/AHA focused update of the Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction (updating the 2007 guideline):a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons [J]. Journal of the American College of Cardiology,2011, 57(19):1920-1959.
[124]Budnitz D. S., Lovegrove M. C., Shehab N., et al. Emergency hospitalizations for adverse drug events in older Americans [J]. The New England journal of medicine, 2011,365(21):2002-2012.
[125]Lenzini P., Wadelius M., Kimmel S., et al. Integration of genetic, clinical, and INR data to refine warfarin dosing [J]. Clinical pharmacology and therapeutics,2010, 87(5):572-578.
[126]Takeuchi F., Mcginnis R., Bourgeois S., et al. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose [J]. PLoS genetics,2009,5(3):e1000433.
[127]Scordo M. G., Pengo V., Spina E., et al. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance [J]. Clinical pharmacology and therapeutics,2002,72(6):702-710.
[128]Rost S., Fregin A., Ivaskevicius V., et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2 [J]. Nature,2004,427(6974): 537-541.
[129]Aquilante C. L., Langaee T. Y., Lopez L. M., et al. Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements [J]. Clinical pharmacology and therapeutics,2006,79(4):291-302.
[130]Cavallari L. H., Langaee T. Y, Momary K. M., et al. Genetic and clinical predictors of warfarin dose requirements in African Americans [J]. Clinical pharmacology and therapeutics,2010,87(4):459-464.
[131]Limdi N. A., Wadelius M., Cavallari L., et al. Warfarin pharmacogenetics:a single VKORC1 polymorphism is predictive of dose across 3 racial groups [J]. Blood, 2010,115(18):3827-3834.
[132]Carlquist J. F., Anderson J. L. Using pharmacogenetics in real time to guide warfarin initiation:a clinician update [J]. Circulation,2011,124(23):2554-2559.
[133]Anderson J. L., Home B. D., Stevens S. M., et al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation [J]. Circulation,2007,116(22):2563-2570.
[134]Caraco Y, Blotnick S., Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation:a prospective randomized controlled study [J]. Clinical pharmacology and therapeutics,2008,83(3): 460-470.
[135]Burmester J. K., Berg R. L., Yale S. H., et al. A randomized controlled trial of genotype-based Coumadin initiation [J]. Genetics in medicine:official journal of the American College of Medical Genetics,2011,13(6):509-518.
[136]Pirmohamed M., Burnside G, Eriksson N., et al. A randomized trial of genotype-guided dosing of warfarin [J]. The New England journal of medicine,2013, 369(24):2294-2303.
[137]Kimmel S. E., French B., Kasner S. E., et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing [J]. The New England journal of medicine,2013, 369(24):2283-2293.
[138]Zineh I., Pacanowski M., Woodcock J. Pharmacogenetics and coumarin dosing--recalibrating expectations [J]. The New England journal of medicine,2013, 369(24):2273-2275.
[139]Gao L., He L., Luo J., et al. Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A [J]. Chinese medical journal,2011, 124(17):2767-2770.
[140]Roth J. A., Boudreau D., Fujii M. M., et al. Genetic Risk Factors for Major Bleeding in Warfarin Patients in a Community Setting [J]. Clinical pharmacology and therapeutics,2014,
[141]Wang M., Lang X., Cui S., et al. Clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality after rheumatic valve replacement:a randomized and controlled trial [J]. International journal of medical sciences,2012,9(6):472-479.
[142]Bruckert E., Hayem G, Dejager S., et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study [J]. Cardiovascular drugs and therapy/sponsored by the International Society of Cardiovascular Pharmacotherapy,2005,19(6):403-414.
[143]Link E., Parish S., Armitage J., et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study [J]. The New England journal of medicine,2008,359(8): 789-799.
[144]Pasanen M. K., Fredrikson H., Neuvonen P. J., et al. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin [J]. Clinical pharmacology and therapeutics,2007,82(6):726-733.
[145]Brunham L. R., Lansberg P. J., Zhang L., et al. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin [J]. The pharmacogenomics journal,2012,12(3):233-237.
[146]Wilke R. A., Ramsey L. B., Johnson S. G., et al. The clinical pharmacogenomics implementation consortium:CPIC guideline for SLCO1B1 and simvastatin-induced myopathy [J]. Clinical pharmacology and therapeutics,2012,92(1):112-117.
[147]Iakoubova O. A., Tong C. H., Rowland C. M., et al. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials:the CARE and WOSCOPS trials [J]. Journal of the American College of Cardiology,2008,51(4):435-443.
[148]Iakoubova O. A., Robertson M., Tong C. H., et al. KIF6 Trp719Arg polymorphism and the effect of statin therapy in elderly patients:results from the PROSPER study [J]. European journal of cardiovascular prevention and rehabilitation official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology,2010, 17(4):455-461.
[149]Ference B. A., Yoo W., Flack J. M., et al. A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol:two meta-analyses and a meta-regression analysis [J]. PloS one,2011,6(12):e28834.
[150]Chasman D. I., Giulianini F., Macfadyen J., et al. Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction:the Justification for the Use of Statins in Prevention:an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial [J]. Circulation Cardiovascular genetics,2012,5(2):257-264.
[151]Trompet S., De Craen A. J., Postmus I., et al. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses [J]. BMC medical genetics,2011,12(131.
[152]Hopewell J. C., Parish S., Offer A., et al. Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study [J]. European heart journal,2013,34(13):982-992.
[153]Shiffman D., Trompet S., Louie J. Z., et al. Genome-wide study of gene variants associated with differential cardiovascular event reduction by pravastatin therapy [J]. PloS one,2012,7(5):e38240.
[154]Chan S. W., Hu M., Tomlinson B. The pharmacogenetics of beta-adrenergic receptor antagonists in the treatment of hypertension and heart failure [J]. Expert opinion on drug metabolism & toxicology,2012,8(7):767-790.
[155]O'connor C. M., Fiuzat M., Carson P. E., et al. Combinatorial pharmacogenetic interactions of bucindolol and betal, alpha2C adrenergic receptor polymorphisms [J]. PloS one,2012,7(10):e44324.
[156]Vandell A. G., Lobmeyer M. T., Gawronski B. E., et al. G protein receptor kinase 4 polymorphisms:beta-blocker pharmacogenetics and treatment-related outcomes in hypertension [J]. Hypertension,2012,60(4):957-964.
[157]Lobmeyer M. T., Gong Y., Terra S. G, et al. Synergistic polymorphisms of betal and alpha2C-adrenergic receptors and the influence on left ventricular ejection fraction response to beta-blocker therapy in heart failure [J]. Pharmacogenetics and genomics, 2007,17(4):277-282.
[158]Schwartz G. L., Turner S. T. Pharmacogenetics of antihypertensive drug responses [J]. American journal of pharmacogenomics:genomics-related research in drug development and clinical practice,2004,4(3):151-160.
[159]Johnson J. A. Advancing management of hypertension through pharmacogenomics [J]. Annals of medicine,2012,44 Suppl 1 (S17-22.
[160]Arnett D. K., Claas S. A. Pharmacogenetics of antihypertensive treatment: detailing disciplinary dissonance [J]. Pharmacogenomics,2009,10(8):1295-1307.
[161]Turner S. T., Bailey K. R., Fridley B. L., et al. Genomic association analysis suggests chromosome 12 locus influencing antihypertensive response to thiazide diuretic [J]. Hypertension,2008,52(2):359-365.
[162]Duarte J. D., Turner S. T., Tran B., et al. Association of chromosome 12 locus with antihypertensive response to hydrochlorothiazide may involve differential YEATS4 expression [J]. The pharmacogenomics journal,2013,13(3):257-263.
[163]Gong Y., Mcdonough C. W., Wang Z., et al. Hypertension susceptibility loci and blood pressure response to antihypertensives:results from the pharmacogenomic evaluation of antihypertensive responses study [J]. Circulation Cardiovascular genetics, 2012,5(6):686-691.
[164]Lifton R. P., Dluhy R. G, Powers M., et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension [J]. Nature,1992,355(6357):262-265.
[165]Hansson J. H., Nelson-Williams C., Suzuki H., et al. Hypertension caused by a truncated epithelial sodium channel gamma subunit:genetic heterogeneity of Liddle syndrome [J]. Nature genetics,1995,11(1):76-82.