高血压相关基因研究进展
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摘要
遗传与基因组医学的进展,催生了精准医疗学科的发展。高血压领域与高血压相关基因研究的进展非常快,主要在三个方面:(1)单基因高血压致病基因的发现,目前至少有17种单基因(或寡基因)高血压,能够找到致病基因,根据致病基因,进行靶向治疗。这一进展目前就可以在临床上推广使用。(2)药物基因组学指导的降压药选择,提高疗效,降低药物副反应,已经显示广阔的前景,如β-受体阻滞剂。但是药物基因组指导的降压药选择,缺乏大规模前瞻性研究,对临床后果影响的研究报告比较少。有待补充这方面的数据。(3)大多数高血压是原发性高血压,多基因,多因素疾病,通过人类全基因组关联分析(GWAS)研究,已经有一些高血压相关遗传变异被发现,但是,所能解释的血压变异非常少,有待进一步研究证明。
Genetic as well as genomic study has advanced the development of precision medicine. We are marching on the road for right patients who are receiving more and more right treatment at right time. In hypertension field, precision medicine is available, actionable and affordable. First and the most practical advancement is monogenic hypertension, the disease-genes have been found for at least 17 types of monogenic hypertension. These patients can be precisely treated according to their carried gene mutation. Secondly, pharmacogenetic and pharmacogenomic guided anti-hypertensive drug selection, very promising but lack of clinic outcome data to support widely clinical application. Majority of hypertension are due to multiple genetic and environmental factors. GWAS fund some genetic variants related to primary hypertension, but these variants can only be responsible for 1-10% of blood pressure variation. We have a long way to go in exploring the real cause of primary hypertension.
Genetic as well as genomic study has advanced the development of precision medicine. We are marching on the road for right patients who are receiving more and more right treatment at right time. In hypertension field, precision medicine is available, actionable and affordable. First and the most practical advancement is monogenic hypertension, the disease-genes have been found for at least 17 types of monogenic hypertension. These patients can be precisely treated according to their carried gene mutation. Secondly, pharmacogenetic and pharmacogenomic guided anti-hypertensive drug selection, very promising but lack of clinic outcome data to support widely clinical application. Majority of hypertension are due to multiple genetic and environmental factors. GWAS fund some genetic variants related to primary hypertension, but these variants can only be responsible for 1-10% of blood pressure variation. We have a long way to go in exploring the real cause of primary hypertension.
引文
[1]Hottenga JJ,Boomsma DI,Kupper N,et al.Heritability and stability of resting blood pressure[J].Twin Res Hum Genet,2005,8(5):499-508.
[2]Miall WE,Oldham PD.The hereditary factor in arterial bloodpressure[J].Br Med J,1963,1(5323):75-80.
[3]Brown MJ.The causes of essential hypertension[J].Br J Clin Pharmacol,1996,42(1):21-27.
[4]Williams RR,Hunt SC,Hopkins PN,et al.Genetic basis of familial dyslipidemia and hypertension:15-year results from Utah[J].Am JHypertens,1993,6(11 Pt 2):319S-327S.
[5]Munroe PB,Barnes MR,Caulfield MJ.Advances in blood pressure genomics[J].Circ Res,2013,112(10):1365-1379.
[6]Ehret GB,Munroe PB,et al.Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk[J].Nature,2011,478(7367):103-109.
[7]Padmanabhan S,Caulfield M,Dominiczak AF.Genetic and molecular aspects of hypertension[J].Circ Res,2015,116(6):937-959.
[8]Wise IA,Charchar FJ.Epigenetic Modifications in Essential Hypertension[J].Int J Mol Sci,2016,17(4):451.
[9]Burrello J,Monticone S,Buffolo F,et al.Is There a Role for Genomics in the Management of Hypertension?[J].International Journal of Molecular Sciences,2017,18(6):1131.
[10]Choi M,Scholl U I,Yue P,et al.K+Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension[J].Science,2011,331(6018):768-772.
[11]Williams TA,Monticone S,Mulatero P.KCNJ5 mutations are the most frequent genetic alteration in primary aldosteronism[J].Hypertension,2015,65(3):507-509.
[12]Fernandes-Rosa FL,Williams TA,Riester A,et al.Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma[J].Hypertension,2014,64(2):354-361.
[13]Monticone S,Else T,Mulatero P,et al.Understanding primary aldosteronism:impact of next generation sequencing and expression profiling[J].Mol Cell Endocrinol,2015,399:311-320.
[14]Daniil G,Fernandes-Rosa FL,Chemin J,et al.CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism[J].EBioMedicine,2016,13:225-236.
[15]Boulkroun S,Samson-Couterie B,Dzib JF,et al.Adrenal cortex remodeling and functional zona glomerulosa hyperplasia in primary aldosteronism[J].Hypertension,2010,56(5):885-892.
[16]Omata K,Anand SK,Hovelson DH,et al.Aldosterone-Producing Cell Clusters Frequently Harbor Somatic Mutations and Accumulate With Age in Normal Adrenals[J].J Endocr Soc,2017,1(7):787-799.
[17]Scholl UI,Goh G,St?lting G,et al.Somatic and germline CACNA1Dcalcium channel mutations in aldosterone-producing adenomas and primary aldosteronism[J].Nat Genet,2013,45(9):1050-1054.
[18]Ulick S,Levine LS,Gunczler P,et al.A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol[J].J Clin Endocrinol Metab,1979,49(5):757-764.
[19]Funder JW.Apparent mineralocorticoid excess[J].J Steroid Biochem Mol Biol,2017,165(Pt A):151-153.
[20]Turcu AF,Auchus RJ.Adrenal steroidogenesis and congenital adrenal hyperplasia[J].Endocrinol Metab Clin,2015,44:275-296.
[21]Biglieri EG,Kater CE.Mineralocorticoids in congenital adrenal hyperplasia[J].J Steroid Biochem Mol Biol,1991,40(4-6):493-499.
[22]Portrat S,Mulatero P,Curnow KM,et al.Deletion hybrid genes,due to unequal crossing over between CYP11B1(11beta-hydroxylase)and CYP11B2(aldosterone synthase)cause steroid 11beta-hydroxylase deficiency and congenital adrenal hyperplasia[J].J Clin Endocrinol Metab,2001,86(7):3197-3201.
[23]Pathare G,Hoenderop JG,Bindels RJ,et al.A molecular update on pseudohypoaldosteronism type II[J].Am J Physiol Renal Physiol,2013,305(11):F1513-F1520.
[24]Rashmi P,Colussi G,Ng M,et al.Glucocorticoid-induced leucine zipper protein regulates sodium and potassium balance in the distal nephron[J].Kidney Int,2017,91(5):1159-1177.
[25]Yang KQ,Lu CX,Xiao Y,et al.A novel frameshift mutation of epithelial sodium channelβ-subunit leads to Liddle syndrome in an isolated case[J].Clin Endocrinol(Oxf),2015,82(4):611-614.
[26]Awadalla M,Patwardhan M,Alsamsam A,et al.Management of Liddle Syndrome in Pregnancy:A Case Report and Literature Review[J].Case Rep Obstet Gynecol,2017,2017:6279460.
[27]Ingelf inger JR.Monogenic and Polygenic Contributions to Hypertension[J].Pediatric Hypertension,2018:113-134.
[28]Liu K,Qin F,Sun X,et al.Analysis of the genes involved in Mendelian forms of low-renin hypertension in Chinese early-onset hypertensive patients[J].J Hypertens,2018,36(3):502-509.
[29]Geller DS,Farhi A,Pinkerton N,et al.Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy[J].Science,2000,289(5476):119-123.
[30]Rafestin-Oblin ME,Souque A,Bocchi B,et al.The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related[J].Endocrinology,2003,144(2):528-533.
[31]Eisenhofer G,Goldstein DS,Kopin IJ,et al.Pheochromocytoma:rediscovery as a catecholamine-metabolizing tumor[J].Endocr Pathol,2003,14(3):193-212.
[32]Lenders JW,Pacak K,Eisenhofer G.New advances in the biochemical diagnosis of pheochromocytoma:moving beyond catecholamines[J].Ann N Y Acad Sci,2002,970:29-40.
[33]Lenders JW,Duh QY,Eisenhofer G,et al.Pheochromocytoma and paraganglioma:an endocrine society clinical practice guideline[J].JClin Endocrinol Metab,2014,99(6):1915-1942.
[34]嗜铬细胞瘤新诊断方法的建立以及SGL-3、SGL-1治疗心力衰竭的药理学研究[D].北京协和医学院,中国医学科学院,清华大学医学部,2009.
[35]Opocher G,Schiav i F.Genetics of pheochromoc y tomas and paragangliomas[J].Best Pract Res Clin Endocrinol Metab,2010,24(6):943-956.
[36]ASCO(American Society of Clinical Oncology).[EB/ON][2018-10-10](2018-02-05)https://www.asco.org/practice-guidelines/cancer.../genetics.../genetic-testing.
[37]Ramachandran R,Rewari V.Current perioperative management of pheochromocytomas[J].Indian J Urol,2017,33(1):19-25.
[38]Torrellas C.Benefits of Pharmacogenetics in the Management of Hypertension[J].Journal of Pharmacogenomics&Pharmacoproteomics,2014,5(2):2-7.
[39]Cars T,Lindhagen L,Malmstr?m RE,et al.Effectiveness of Drugs in Routine Care:A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example[J].Clin Pharmacol Ther,2018,103(3):493-501.
[40]Fan X,Wang Y,Sun K,et al.Polymorphisms of ACE2 Gene are Associated With Essential Hypertension and Antihypertensive Effects of Captopril in Women[J].Clinical Pharmacology&Therapeutics,2007,82(2):187-196.
[41]Spear,trends in Medicine 2001:7(5),and A spinall,ACMGPresentation March 13,2008 National Vital Statistics Reports 2005:53(17)-US Data from 2001
[42]Phi l l ips KA,Veenstra DL,Oren E,et al.Potent ial role of pharmacogenomics in reducing adverse drug reactions:a systematic review[J].JAMA,2001,286(18):2270-2279.
[43]NICE:Hypertension in adults:diagnosis and management.Clinical guideline[CG127]Published date:August 2011 Last updated:November 2016,guidance.nice.org.uk/CG127.
[44]Carey RM,W helton PK.Prevention,Detection,Evaluation,and Management of High Blood Pressure in Adults:Synopsis of the2017 American College of Cardiology/American Heart Association Hypertension Guideline[J].Ann Intern Med,2018,168(5):351-358.
[45]Bryan W,Giuseppe M,Wilko S,et al.2018 ESC/ESH Guidelines for the management of arterial hypertension[J].Eur Heart J,2018,39(33):3021-3104.
[46]Butalia S,Audibert F,C?téAM,et al.Hypertension Canada's 2018Guidelines for the Management of Hypertension in Pregnancy[J].Can J Cardiol,2018,34(5):526-531.
[47]Elbein S,Gamazon E,Das S,et al.Genetic Risk Factors for Type 2Diabetes:A Trans-Regulatory Genetic Architecture?[J].The American Journal of Human Genetics,2012,91(3):466-477.
[48]Cooper-DeHoff RM,Johnson JA.Hypertension pharmacogenomics:in search of personalized treatment approaches[J].Nat Rev Nephrol,2016,12(2):110-122.
[49]Eadon MT,Kanuri SH,Chapman AB.Pharmacogenomic studies of hypertension:paving the way for personalized antihypertensive treatment[J].Expert Review of Precision Medicine and Drug Development,2018,3(1):33-47.
[50]Genovese G,Friedman DJ,Ross MD,et al.Association of trypanolytic ApoL1 variants with kidney disease in African Americans[J].Science,2010,329(5993):841-845.DOI:10.1126/science.1193032.
[51]Tzur S,Rosset S,Shemer R,et al.Missense mutations in the APOL1gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene[J].Hum Genet,2010,128(3):345-350.
[52]Bruggeman LA,O'Toole JF,Sedor JR.APOL1 polymorphisms and kidney disease:loss-of-function or gain-of-function[J].Am J Physiol Renal Physiol,2019,316(1):F1-F8.
[53]Mukamal KJ,Tremaglio J,Friedman DJ,et al.APOL1 Genotype,Kidney and Cardiovascular Disease,and Death in Older Adults[J].Arterioscler Thromb Vasc Biol,2016,36(2):398-403.
[54]Calhoun DA,Jones D,Textor S,et al.Resistant hypertension:diagnosis,evaluation,and treatment:a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research[J].Circulation,2008,117(25):e510-e526.
[55]Matteo T,Sylvie J,Chiara L,et al.Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression.[J].Nature medicine,2013(12):1655-1660.
[56]Graham L A,Padmanabhan S,Fraser NJ,et al.Validation of uromodulin as a candidate gene for human essential hypertension[J].Hypertension,2014,63(3):551-558.
[57]Padmanabhan S,Melander O,Johnson T,et al.Genome wide association study of blood pressure extremes identifies variant in umod associated with hypertension:6B.01[J].Journal of Hypertension,2010,28:e237.
[58]Lopes LB,Abreu CC,Souza CF,et al.Identification of a novel UMODmutation(c.163G>A)in a Brazilian family with autosomal dominant tubulointerstitial kidney disease[J].Revista brasileira de pesquisas medicas e biologicas,2018,51(3):e6560.
[59]Ga r b e r A M.A n u n c e r t a i n f u t u re f o r c a rd i ov a s c u l a r d r u g development[J].N Engl J Med,2009,360(12):1169-1171.
[60]Levy D,Ehret GB,Rice K,et al.Genome-wide association study of blood pressure and hypertension[J].Nat Genet,2009,41(6):677-687.
[61]Georg Ehret,Patricia B Munroe,Kenneth Rice,et al.Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.Nature 2011,478,103-109.
[62]Ehret GB,Caulfield MJ.Genes for blood pressure:an opportunity to understand hypertension[J].Eur Heart J,2013,34(13):951-961.
[63]Ji Y,Skierka JM,Blommel JH,et al.Preemptive Pharmacogenomic Testing for Precision Medicine:A Comprehensive Analysis of Five Actionable Pharmacogenomic Genes Using Next-Generation DNASequencing and a Customized CYP2D6 Genotyping Cascade[J].JMol Diagn,2016,18(3):438-445.
[64]Haga SB.Integrating pharmacogenetic testing into primary care[J].Expert Review of Precision Medicine and Drug Development,2017,2(6):327-336.
[2]Miall WE,Oldham PD.The hereditary factor in arterial bloodpressure[J].Br Med J,1963,1(5323):75-80.
[3]Brown MJ.The causes of essential hypertension[J].Br J Clin Pharmacol,1996,42(1):21-27.
[4]Williams RR,Hunt SC,Hopkins PN,et al.Genetic basis of familial dyslipidemia and hypertension:15-year results from Utah[J].Am JHypertens,1993,6(11 Pt 2):319S-327S.
[5]Munroe PB,Barnes MR,Caulfield MJ.Advances in blood pressure genomics[J].Circ Res,2013,112(10):1365-1379.
[6]Ehret GB,Munroe PB,et al.Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk[J].Nature,2011,478(7367):103-109.
[7]Padmanabhan S,Caulfield M,Dominiczak AF.Genetic and molecular aspects of hypertension[J].Circ Res,2015,116(6):937-959.
[8]Wise IA,Charchar FJ.Epigenetic Modifications in Essential Hypertension[J].Int J Mol Sci,2016,17(4):451.
[9]Burrello J,Monticone S,Buffolo F,et al.Is There a Role for Genomics in the Management of Hypertension?[J].International Journal of Molecular Sciences,2017,18(6):1131.
[10]Choi M,Scholl U I,Yue P,et al.K+Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension[J].Science,2011,331(6018):768-772.
[11]Williams TA,Monticone S,Mulatero P.KCNJ5 mutations are the most frequent genetic alteration in primary aldosteronism[J].Hypertension,2015,65(3):507-509.
[12]Fernandes-Rosa FL,Williams TA,Riester A,et al.Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma[J].Hypertension,2014,64(2):354-361.
[13]Monticone S,Else T,Mulatero P,et al.Understanding primary aldosteronism:impact of next generation sequencing and expression profiling[J].Mol Cell Endocrinol,2015,399:311-320.
[14]Daniil G,Fernandes-Rosa FL,Chemin J,et al.CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism[J].EBioMedicine,2016,13:225-236.
[15]Boulkroun S,Samson-Couterie B,Dzib JF,et al.Adrenal cortex remodeling and functional zona glomerulosa hyperplasia in primary aldosteronism[J].Hypertension,2010,56(5):885-892.
[16]Omata K,Anand SK,Hovelson DH,et al.Aldosterone-Producing Cell Clusters Frequently Harbor Somatic Mutations and Accumulate With Age in Normal Adrenals[J].J Endocr Soc,2017,1(7):787-799.
[17]Scholl UI,Goh G,St?lting G,et al.Somatic and germline CACNA1Dcalcium channel mutations in aldosterone-producing adenomas and primary aldosteronism[J].Nat Genet,2013,45(9):1050-1054.
[18]Ulick S,Levine LS,Gunczler P,et al.A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol[J].J Clin Endocrinol Metab,1979,49(5):757-764.
[19]Funder JW.Apparent mineralocorticoid excess[J].J Steroid Biochem Mol Biol,2017,165(Pt A):151-153.
[20]Turcu AF,Auchus RJ.Adrenal steroidogenesis and congenital adrenal hyperplasia[J].Endocrinol Metab Clin,2015,44:275-296.
[21]Biglieri EG,Kater CE.Mineralocorticoids in congenital adrenal hyperplasia[J].J Steroid Biochem Mol Biol,1991,40(4-6):493-499.
[22]Portrat S,Mulatero P,Curnow KM,et al.Deletion hybrid genes,due to unequal crossing over between CYP11B1(11beta-hydroxylase)and CYP11B2(aldosterone synthase)cause steroid 11beta-hydroxylase deficiency and congenital adrenal hyperplasia[J].J Clin Endocrinol Metab,2001,86(7):3197-3201.
[23]Pathare G,Hoenderop JG,Bindels RJ,et al.A molecular update on pseudohypoaldosteronism type II[J].Am J Physiol Renal Physiol,2013,305(11):F1513-F1520.
[24]Rashmi P,Colussi G,Ng M,et al.Glucocorticoid-induced leucine zipper protein regulates sodium and potassium balance in the distal nephron[J].Kidney Int,2017,91(5):1159-1177.
[25]Yang KQ,Lu CX,Xiao Y,et al.A novel frameshift mutation of epithelial sodium channelβ-subunit leads to Liddle syndrome in an isolated case[J].Clin Endocrinol(Oxf),2015,82(4):611-614.
[26]Awadalla M,Patwardhan M,Alsamsam A,et al.Management of Liddle Syndrome in Pregnancy:A Case Report and Literature Review[J].Case Rep Obstet Gynecol,2017,2017:6279460.
[27]Ingelf inger JR.Monogenic and Polygenic Contributions to Hypertension[J].Pediatric Hypertension,2018:113-134.
[28]Liu K,Qin F,Sun X,et al.Analysis of the genes involved in Mendelian forms of low-renin hypertension in Chinese early-onset hypertensive patients[J].J Hypertens,2018,36(3):502-509.
[29]Geller DS,Farhi A,Pinkerton N,et al.Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy[J].Science,2000,289(5476):119-123.
[30]Rafestin-Oblin ME,Souque A,Bocchi B,et al.The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related[J].Endocrinology,2003,144(2):528-533.
[31]Eisenhofer G,Goldstein DS,Kopin IJ,et al.Pheochromocytoma:rediscovery as a catecholamine-metabolizing tumor[J].Endocr Pathol,2003,14(3):193-212.
[32]Lenders JW,Pacak K,Eisenhofer G.New advances in the biochemical diagnosis of pheochromocytoma:moving beyond catecholamines[J].Ann N Y Acad Sci,2002,970:29-40.
[33]Lenders JW,Duh QY,Eisenhofer G,et al.Pheochromocytoma and paraganglioma:an endocrine society clinical practice guideline[J].JClin Endocrinol Metab,2014,99(6):1915-1942.
[34]嗜铬细胞瘤新诊断方法的建立以及SGL-3、SGL-1治疗心力衰竭的药理学研究[D].北京协和医学院,中国医学科学院,清华大学医学部,2009.
[35]Opocher G,Schiav i F.Genetics of pheochromoc y tomas and paragangliomas[J].Best Pract Res Clin Endocrinol Metab,2010,24(6):943-956.
[36]ASCO(American Society of Clinical Oncology).[EB/ON][2018-10-10](2018-02-05)https://www.asco.org/practice-guidelines/cancer.../genetics.../genetic-testing.
[37]Ramachandran R,Rewari V.Current perioperative management of pheochromocytomas[J].Indian J Urol,2017,33(1):19-25.
[38]Torrellas C.Benefits of Pharmacogenetics in the Management of Hypertension[J].Journal of Pharmacogenomics&Pharmacoproteomics,2014,5(2):2-7.
[39]Cars T,Lindhagen L,Malmstr?m RE,et al.Effectiveness of Drugs in Routine Care:A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example[J].Clin Pharmacol Ther,2018,103(3):493-501.
[40]Fan X,Wang Y,Sun K,et al.Polymorphisms of ACE2 Gene are Associated With Essential Hypertension and Antihypertensive Effects of Captopril in Women[J].Clinical Pharmacology&Therapeutics,2007,82(2):187-196.
[41]Spear,trends in Medicine 2001:7(5),and A spinall,ACMGPresentation March 13,2008 National Vital Statistics Reports 2005:53(17)-US Data from 2001
[42]Phi l l ips KA,Veenstra DL,Oren E,et al.Potent ial role of pharmacogenomics in reducing adverse drug reactions:a systematic review[J].JAMA,2001,286(18):2270-2279.
[43]NICE:Hypertension in adults:diagnosis and management.Clinical guideline[CG127]Published date:August 2011 Last updated:November 2016,guidance.nice.org.uk/CG127.
[44]Carey RM,W helton PK.Prevention,Detection,Evaluation,and Management of High Blood Pressure in Adults:Synopsis of the2017 American College of Cardiology/American Heart Association Hypertension Guideline[J].Ann Intern Med,2018,168(5):351-358.
[45]Bryan W,Giuseppe M,Wilko S,et al.2018 ESC/ESH Guidelines for the management of arterial hypertension[J].Eur Heart J,2018,39(33):3021-3104.
[46]Butalia S,Audibert F,C?téAM,et al.Hypertension Canada's 2018Guidelines for the Management of Hypertension in Pregnancy[J].Can J Cardiol,2018,34(5):526-531.
[47]Elbein S,Gamazon E,Das S,et al.Genetic Risk Factors for Type 2Diabetes:A Trans-Regulatory Genetic Architecture?[J].The American Journal of Human Genetics,2012,91(3):466-477.
[48]Cooper-DeHoff RM,Johnson JA.Hypertension pharmacogenomics:in search of personalized treatment approaches[J].Nat Rev Nephrol,2016,12(2):110-122.
[49]Eadon MT,Kanuri SH,Chapman AB.Pharmacogenomic studies of hypertension:paving the way for personalized antihypertensive treatment[J].Expert Review of Precision Medicine and Drug Development,2018,3(1):33-47.
[50]Genovese G,Friedman DJ,Ross MD,et al.Association of trypanolytic ApoL1 variants with kidney disease in African Americans[J].Science,2010,329(5993):841-845.DOI:10.1126/science.1193032.
[51]Tzur S,Rosset S,Shemer R,et al.Missense mutations in the APOL1gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene[J].Hum Genet,2010,128(3):345-350.
[52]Bruggeman LA,O'Toole JF,Sedor JR.APOL1 polymorphisms and kidney disease:loss-of-function or gain-of-function[J].Am J Physiol Renal Physiol,2019,316(1):F1-F8.
[53]Mukamal KJ,Tremaglio J,Friedman DJ,et al.APOL1 Genotype,Kidney and Cardiovascular Disease,and Death in Older Adults[J].Arterioscler Thromb Vasc Biol,2016,36(2):398-403.
[54]Calhoun DA,Jones D,Textor S,et al.Resistant hypertension:diagnosis,evaluation,and treatment:a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research[J].Circulation,2008,117(25):e510-e526.
[55]Matteo T,Sylvie J,Chiara L,et al.Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression.[J].Nature medicine,2013(12):1655-1660.
[56]Graham L A,Padmanabhan S,Fraser NJ,et al.Validation of uromodulin as a candidate gene for human essential hypertension[J].Hypertension,2014,63(3):551-558.
[57]Padmanabhan S,Melander O,Johnson T,et al.Genome wide association study of blood pressure extremes identifies variant in umod associated with hypertension:6B.01[J].Journal of Hypertension,2010,28:e237.
[58]Lopes LB,Abreu CC,Souza CF,et al.Identification of a novel UMODmutation(c.163G>A)in a Brazilian family with autosomal dominant tubulointerstitial kidney disease[J].Revista brasileira de pesquisas medicas e biologicas,2018,51(3):e6560.
[59]Ga r b e r A M.A n u n c e r t a i n f u t u re f o r c a rd i ov a s c u l a r d r u g development[J].N Engl J Med,2009,360(12):1169-1171.
[60]Levy D,Ehret GB,Rice K,et al.Genome-wide association study of blood pressure and hypertension[J].Nat Genet,2009,41(6):677-687.
[61]Georg Ehret,Patricia B Munroe,Kenneth Rice,et al.Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.Nature 2011,478,103-109.
[62]Ehret GB,Caulfield MJ.Genes for blood pressure:an opportunity to understand hypertension[J].Eur Heart J,2013,34(13):951-961.
[63]Ji Y,Skierka JM,Blommel JH,et al.Preemptive Pharmacogenomic Testing for Precision Medicine:A Comprehensive Analysis of Five Actionable Pharmacogenomic Genes Using Next-Generation DNASequencing and a Customized CYP2D6 Genotyping Cascade[J].JMol Diagn,2016,18(3):438-445.
[64]Haga SB.Integrating pharmacogenetic testing into primary care[J].Expert Review of Precision Medicine and Drug Development,2017,2(6):327-336.