原发性高血压病eNOS基因G894T变异与超重及腰臀比异常交互作用研究
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摘要
目的探讨eNOS基因G894T变异和AGT基因M235T变异与超重及腰臀比异常之间的交互作用对原发性高血压的影响。
方法以青岛市区四个社区人群健康查体中筛检出的、未经药物系统治疗的235名原发性高血压患者及240名正常血压者为调查对象;用聚合酶链反应—限制性片段长度多态性(PCR—RFLP)方法检测eNOS基因G894T多态性及AGT基因M235T多态性;用相加模型分别分析基因多态性变异与超重及腰臀比异常之间的交互作用。
结果高血压组eNOS基因T等位基因频率(18.94%)及AGT基因T等位基因频率(46.81%)高于对照组(12.71%,37.71%),(χ~2=6.927,8.677,P＜0.01);高血压组超重率(86.81%)及腰臀比异常率(69.79%)高于对照组(70.83%,47.92%),(χ~2=18.100,23.433,P＜0.001)。
用多因素Logistic回归调整年龄、性别、体质指数、吸烟及饮酒、血脂等混杂因素后,eNOS基因G894T基因变异与腰臀比异常间存在正交互作用,其协同效应指数(S)为1.542,归因交互效应[I(AB)]为0.909,归因交互效应百分比(AP%)为25.34%,纯因子间归因交互效应百分比(AP~*%)为35.14%;AGT基因T等位基因与腰臀比异常亦有正交互作用,调整上述混杂因素后其以上指数分别为1.930、1.560、36.82%、48.19%;AGT基因T等位基因与超重亦有正交互作用,调整混杂后其以上指数分别为2.241、0.598、28.75%、55.37%。此外,eNOS基因T等位基因与AGT基因T等位基因亦有正交互作用,调整混杂后其以上指数分别为1.600、1.520、30.07%、37.48%。
结论eNOS基因T等位基因、AGT基因T等位基因、超重与腰臀比异常是原发性高血压发生的危险因素;eNOS基因T等位基因、AGT基因T等位基因与腰臀比异常之间的交互作用在该研究人群高血压患病中具有重要意义。在携带eNOS基因T等位基因或AGT基因T等位基因同时伴有腰臀比异常的人群中,控制腰臀比异常可明显降低居民原发性高血压患病的危险性。
Objective To analyze the effects of G894T(Glu298Asp) mutation in eNOS gene, M235T mutation in AGT gene and abnormality of waist-to-hip ratio(WHR),overweight and the interactions between the four factors on essential hypertension(EH).
Methods The study population came from a screening survey carried out in four communities in Qingdao.A total of 235 patients diagnosed as essential hypertension, without anti-hypertensive medication,and 240 healthy subjects were enrolled in the current study.Polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP) were performed to detect the polymorphism of G894T in the endothelial nitric oxide synthase(eNOS ) gene and M235T in the angiotensinogen(AGT) gene.Additive model was used to analyze the interactions between these genes and overweight or abnormal Waist-to-Hip Ratio(WHR).
Results eNOS gene T allele frequency(18.94%) and AGT gene T allele frequency (46.81%) in patients were significantly higher than those in controls(12.71%, 37.71%),(χ~2=6.927,8.677,P＜0.01 );The frequency of overweight(86.81%) and frequency of abnormality of WHR(69.79%) in patients were significantly higher than those in controls(70.83%,47.92%),(χ~2=18.100,23.433,P＜0.001).
After adjusting age,gender,drinking,smoking,body mass index and blood fats by logistic regression,G894T mutation of eNOS gene and abnormality of WHR showed a positive interaction.Synergy index between the G894T mutation in eNOS gene and Abnormality of WHR was 1.542,attributable interaction was 0.909,attributable interaction percentage was 25.34%,pure attributable interaction percentage was 35.14 %.M235T mutation of AGT gene and abnormality of WHR also showed a positive interaction.After adjusting the confounding factors mentioned above by logistic regression,the indexes mentioned above were 1.930,1.560,36.82%and 48.19% respectively.There was also a positive interaction between M235T mutation in AGT gene and overweight,the indexes were 2.241,0.598,28.75%and 55.37%respectively after adjustment of confounding factors by logistic regression.In addition,there was also a positive interaction between polymorphisms of T allele of eNOS and T allele of AGT,the indexes were 1.600,1.520,30.07%and 37.48%respectivelyafter adjustment of confounding factors by logistic regression.
Conclusions T allele of eNOS,T allele of AGT,overweight and abnormality of WHR were the risk factors of essential hypertension.The interactions among T allele of eNOS,T allele of AGT and abnormality of WHR had positive effects on essential hypertension in this studied population.To control abnormality of WHR in the population who had T allele of eNOS or T allele of AGT and abnormality of WHR simultaneously could produce marked decrease of getting essential hypertension in general population.
方法以青岛市区四个社区人群健康查体中筛检出的、未经药物系统治疗的235名原发性高血压患者及240名正常血压者为调查对象;用聚合酶链反应—限制性片段长度多态性(PCR—RFLP)方法检测eNOS基因G894T多态性及AGT基因M235T多态性;用相加模型分别分析基因多态性变异与超重及腰臀比异常之间的交互作用。
结果高血压组eNOS基因T等位基因频率(18.94%)及AGT基因T等位基因频率(46.81%)高于对照组(12.71%,37.71%),(χ~2=6.927,8.677,P＜0.01);高血压组超重率(86.81%)及腰臀比异常率(69.79%)高于对照组(70.83%,47.92%),(χ~2=18.100,23.433,P＜0.001)。
用多因素Logistic回归调整年龄、性别、体质指数、吸烟及饮酒、血脂等混杂因素后,eNOS基因G894T基因变异与腰臀比异常间存在正交互作用,其协同效应指数(S)为1.542,归因交互效应[I(AB)]为0.909,归因交互效应百分比(AP%)为25.34%,纯因子间归因交互效应百分比(AP~*%)为35.14%;AGT基因T等位基因与腰臀比异常亦有正交互作用,调整上述混杂因素后其以上指数分别为1.930、1.560、36.82%、48.19%;AGT基因T等位基因与超重亦有正交互作用,调整混杂后其以上指数分别为2.241、0.598、28.75%、55.37%。此外,eNOS基因T等位基因与AGT基因T等位基因亦有正交互作用,调整混杂后其以上指数分别为1.600、1.520、30.07%、37.48%。
结论eNOS基因T等位基因、AGT基因T等位基因、超重与腰臀比异常是原发性高血压发生的危险因素;eNOS基因T等位基因、AGT基因T等位基因与腰臀比异常之间的交互作用在该研究人群高血压患病中具有重要意义。在携带eNOS基因T等位基因或AGT基因T等位基因同时伴有腰臀比异常的人群中,控制腰臀比异常可明显降低居民原发性高血压患病的危险性。
Objective To analyze the effects of G894T(Glu298Asp) mutation in eNOS gene, M235T mutation in AGT gene and abnormality of waist-to-hip ratio(WHR),overweight and the interactions between the four factors on essential hypertension(EH).
Methods The study population came from a screening survey carried out in four communities in Qingdao.A total of 235 patients diagnosed as essential hypertension, without anti-hypertensive medication,and 240 healthy subjects were enrolled in the current study.Polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP) were performed to detect the polymorphism of G894T in the endothelial nitric oxide synthase(eNOS ) gene and M235T in the angiotensinogen(AGT) gene.Additive model was used to analyze the interactions between these genes and overweight or abnormal Waist-to-Hip Ratio(WHR).
Results eNOS gene T allele frequency(18.94%) and AGT gene T allele frequency (46.81%) in patients were significantly higher than those in controls(12.71%, 37.71%),(χ~2=6.927,8.677,P＜0.01 );The frequency of overweight(86.81%) and frequency of abnormality of WHR(69.79%) in patients were significantly higher than those in controls(70.83%,47.92%),(χ~2=18.100,23.433,P＜0.001).
After adjusting age,gender,drinking,smoking,body mass index and blood fats by logistic regression,G894T mutation of eNOS gene and abnormality of WHR showed a positive interaction.Synergy index between the G894T mutation in eNOS gene and Abnormality of WHR was 1.542,attributable interaction was 0.909,attributable interaction percentage was 25.34%,pure attributable interaction percentage was 35.14 %.M235T mutation of AGT gene and abnormality of WHR also showed a positive interaction.After adjusting the confounding factors mentioned above by logistic regression,the indexes mentioned above were 1.930,1.560,36.82%and 48.19% respectively.There was also a positive interaction between M235T mutation in AGT gene and overweight,the indexes were 2.241,0.598,28.75%and 55.37%respectively after adjustment of confounding factors by logistic regression.In addition,there was also a positive interaction between polymorphisms of T allele of eNOS and T allele of AGT,the indexes were 1.600,1.520,30.07%and 37.48%respectivelyafter adjustment of confounding factors by logistic regression.
Conclusions T allele of eNOS,T allele of AGT,overweight and abnormality of WHR were the risk factors of essential hypertension.The interactions among T allele of eNOS,T allele of AGT and abnormality of WHR had positive effects on essential hypertension in this studied population.To control abnormality of WHR in the population who had T allele of eNOS or T allele of AGT and abnormality of WHR simultaneously could produce marked decrease of getting essential hypertension in general population.
引文
[1]张东峰,许小幸,高维主.青岛农村居民对高血压的知晓率、服药率及影响因素的分析[J].卫生研究,2001,30(2):100-102
[2]王文鹃,王克安,李大麟,等.体质指数、腰围和腰臀比预测高血压、高血糖的实用价值及其建议值探讨[J].中华流行病学杂志,2002,23(1):16-19
[3]Shoji M,Tsutaya S,Satio R,etal.Positive association of endothelial nitric oxide synthase gene polymorphism with hypertension in northern Japan[J].Life Sci,2000.66:2557-2562.
[4]Miyamoto Y,Satio Y,Kajiyama N,etal.Endothelial nitric oxide sythase gene is positively associated with essential hypertension[J].Hypertension,1998,32:3-8.
[5]Kishimoto T,Misawa Y,Kaetu A,et al.eNOS Glu298Asp polymorphism and hypertension in a cohort study in Japanese[J].Preventive Medicine 39(2004) 927-931.
[6]Jeunematir X,Soubrier F,Kotelevtser Y,et al.Molecular basis of human hypertension:role of angiotensinogen[J].Cell,1992,71:169-180
[7]Sethi AA,Nordestgaard BG,Agerholm-Larsen B,et al.Angiotensinogen polymorphisms and elevated blood pressure in the general population:the Copenhagen city heart study[J].Hypertension,2001,37(1):875-881
[8]Sato N,Katsuya T,Nakagawa T,et al.Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension[J].Life Sci,2000(68):259-272
[9]Jeunemaitre X,Inoue I,Williams C,et al.Haplotypes ofangiotensinogen inessential hypertension[J].Am J Hum Genet,1997(60):1448-1460
[10]Hegele RA,Brunt JH,Connelly PW.Genetic and biochemical factors associated with variation in blood pressure in a genetic isolate[J].Hypertension,1996,27:308-312
[11]Formiguera X,Canto'n A.Obesity:epidemiology and clinical aspects[J].Best Practice &Research Clinical Gastroenterology.2004.Vol.18,No.6,pp:1125-1146.
[12]Carlos A.Feldstein,Maia Akopian,etal.A comparison of body mass index and waist-to-hip ratio as indicators of hypertension risk in an urban Argentine population:A hospital-based study[J].Nutrition,Metabolism & Cardiovascular Diseases(2005) 15,310-315.
[13]周和,陈思东,张信,等。中年知识分子体重指数、腰围及腰臀比与高血压发生的风险性分析[J]。广州医学院学报,2004,March,32(1):55-59,62。
[14]叶浩风,赵小兵,吴伟峰,等.农村居民高血压与体质指数、腰臀比关系的研究[J]。职业与健康,2005,21(9):1288.1290.
[15]石学香,逢增昌,汪韶洁,等.青岛市成人体质指数及其腰围与高血压的关系[J].中国慢性病预防与控制,2006,14(6):444-445。
[16]Ishigami T,Umemura S,Wamoto T,Tamura K,Hibi K,Yamaguchi S,etal.Molecular variant ofangiotensinogen(AGT) gene is associated with coronary atherosclerosis[J].Circulation,1995,91(4):951-954.
[17]贾崇奇,赵仲堂,王立华,等。一氧化氮合酶基因G894T变异与高血压病关系的研究[J]。中华流行病杂志,2003,24(1):677-680。
[18]Shoji M,Tsutaya S,Satio R,etal.Positive association of endothelial nitric oxide synthase gene polymorphism with hypertension in northern Japarl[J].Life Sci,2000.66:2557-2562.
[19]李东宝,华琦,皮林。内皮性一氧化氮合酶基因G894T多态性与与原发性高血压的相关关系[J]。高血压杂志,2004,Aug,12(4):326-330。
[20]张丽萍,汪师贞,赵学信,等。内皮型一氧化氮合酶基因G894T多态性与新疆维吾尔族原发性高血压的关联研究[J]。中华心血管病杂志,2006,May,34(5):403-406。
[21]王琳,陈丹,薛雨,等。内皮型一氧化氮合酶基因Glu298Asp多态性与原发性高血压的关系[J]。国际遗传学杂志,2006,Oct,29(5):336-340。
[22]Zhao Qi,Su Shao-yong,Chen Shu-feng.Association study of the endothelial nitric oxide synthasegene polymorphisms with essential hypertension in northern Han Chinese[J].Chinese Medical Journal 2006;119(13):1065-1071.
[23]Jeunemaitre X,Soubrier F,Kotelevtsev YV,et al.Molecular basis of human hypertension:Role ofangiotensinogen[J].Cell,1992,71(1):169-180.
[24]Yee-How Say,King-Hwa Ling,Gnanasothie Duraisamy.Angiotensinogen M235T gene variants and its association with essential hypertension and plasma renin activity in Malaysian subjects:A case control study[J].BMC Cardiovascular Disorders.2005,5:7.
[25]孙琦,柳青,雷寒。血管紧张素原M235T基因多态性与重庆地区原发性高血压的关系[J]。重庆医学,2002,November,31(11):1072-1073。
[26]蔡思宇,俞峰,施育平。血管紧张素原M235T基因多态性与原发性高血压的相关研究[J]。浙江大学学报(医学版),2004,33(2):151-154。
[27]Adrian Mondry,Marie Loh,Pengbo Liu,Ai-Ling Zhu.Polymorphisms of the insertion /deletion ACE and M235T AGT genes and hypertension:surprising new findings and meta-analysis of data[J].BMC Nephrology 2005,6:1.
[28]Wenquan NIU,Yue QI,Weijun CEN.Genetic Polymorphisms of Angiotensinogen and Essential Hypertension in a Tibetan Population[J].Hypertens Res Vol.30,No.11(2007):1129-1137
[29]BARBARA NEMESURE,SUH-YUH WU,ANSELM HENNIS.The Relationship of Body Mass Index and Waist-Hip Ratio on the 9-Year Incidence of Diabetes and Hypertension in a Predominantly African-origin Population[J].AEP Vol.18,No.8 August 2008:657-663
[30]Witteman JC,Willett WC,Stampfer MJ,etal.Aprospetive study of nutritiona 1 factors and hypertension among US women[J].Circulation,1989,80:1320-1327
[31]孙蓉,顾建建,孙峰。江苏省自然人群高血压患病率及相关因素分析[J]。江苏临床医学杂志,2002年第6(6):534-536
[32]王薇,吴兆苏,刘静,等。11省市自然人群原发性高血压患病率及相关因素的流行病学研究[J]。心脑血管病杂志,1998,17(2):81
[33]Kuschnir MC,Mendonca GA.Risk factors associated with arterial hypertension in adolescents[J].J Pediatr(Rio J).2007,83(4):335-342
[34]陈晓荣,汪韶洁,逢增昌,等.青岛市城乡部分中老年人肥胖现况调查[J]。预防医学文献息,2003,9(6):671-672
[35]周晓红,路方红,金世宽等。血管紧张素原M235T基因多态性及体重指数与原发性高血压的关系[J]。中国老年学杂志,2008,May,28(9):875-877
[1]Ismail M,Akhtar N,Nasir M,et al Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and essential hypertension in young Pakistani patients[J].Biochem Mol Biol,2004,37(5):552-5.
[2]巩云霞,庞小芬,朱理敏,等。ACE基因多态性与老年人原发性高血压的关系[J]。实用老年医学。2001,15(5):115-121.
[3]Markovic D,Tang X,Guruju M,et al.Association of angiotensinogen gene polymorphism with essential hypertension in African-Americans and Caucasians[J].Hum Hered,2005,60(2):89-96.
[4]Jain S,Li Y,Patil S,et al A single-nucleotide polymorphism in human angiotensinogen gene is associated with essential hypertension and affects glucocorticoid induced promoter activity[J].Mol Med,2005,83(2):121-131.
[5]Tsai CT,Falin D,Chiang FT,et al.Angiotensinogen gene haplotype and hypertension[J].Hypertens,2003,41:9215.
[6]Renner W,Nauck M,Winkelmann BR,et al.Assotiation of angiotensinogen haplotypes with angiotensinogen levels but not with blood pressure or coronary artery disease[J],the Ludwigshafen Ridk and Cardiovascular Heath Study.Mol,2005,83(3):235-239.
[7]Yanai K,Nibu Y,Murakami K et al.A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequencea in human angiontensinogen gene[J].J Biol Chem,1996,271(27):15981-15986.
[8]Brand Herrmann SM,Kopke K,Reichenberger F et al.Angiotensinogen promoter haplotypes are associated with blood pressure in untreated hypertensives[J].Hypertens,2004,22(7):1289-1292.
[9]Vasku A,Soucek M,Tahoplova S et al.An association of BMI with A(-6) G,M235T and T174M polymorphisms in angiotensinogen gene in essential hypertension[J].Hum Hypertens,2002,16(6):427-430.
[10]Frossard PM,Lestingany GG,Malloy MJ,et al.Human rennin gene dimorphism associated with hypertension in two independent populations[J].Clin Genet,1999,56(6):428.
[11]Asai,Masayoshi Soma,Shinichiro Kokubun et al.Haplotype Analysis of the human renin Gene and Essential Hypertension[J].Hypertension,2003,41:308-312.
[12]Chiang FT Hsu KL,Tseng CD,et al.Association of the rennin gene polymorphism with essential hypertension in a Chinese population[J].Clin Genet,1997,51(6):370.
[13]宋卫华 党爱民等。原发性高血压相关基因研究进展[J]。Molecular Cardiology of China, April 2005,Vol 5.No 2.Serial No 21.
[14]Henderson SO,Naiman CA,Mack W.Mutiple polymorphisms in the rennin-aldosterone system(ACE,CYP11B2,AGTR1 ) and their contribution to hypertension in African Americans and Lations in the multienthnic cohort.Am J Med Sci,2004,328(5):266-273.
[15]Kotanko P,Binder A,Tasher Jet al,Essential hypertension in African Caribbeans with a variants of the beta2-adrenoceptor[J].Hypertension,1997,30(4):773-776.
[16]Jindra A.Horkyk,Peleska Jet al.Association analysis of Arg 16 Gly polymorphism of the beta2-adrenergic receptor gene in offspring from hypertension and normotensive families[J].Blood press.2002,11(4):213-217.
[17]Herrmann SM,Nicaud V,Triet Let al.Polymorphisms of the beta2-adrenoceptor(ADRB2)gene and essential hypertension:the ECTIM and PEGASE Studies[J].Hypertension,2002,20(2):229-235.
[18]Tomaszewski M,Brain N J,charchar FJ et al.Essential hypertension and beta2-adrenergic receptor-gene;linkage and association[J].Hypertension.2002,40(3):286-291.
[19]Braun A,Maier S,Kammerer Set al.A novel sequence polymorphism in the promoter region of the human β2 bradykinin receptor gene[J].Hum Genet,1996,97:688,689.
[20]Tomaszewski M,Brain N J,Charchar FJ etal.Essential hypertension and beta2-adrenergic recetor gene;linkage and association[J].Hypertension,2002,40(3):286-291.
[21]Braun A,Maier S,Kammerer Set al.A novel sequence polymorphism in the promoter region of the human 132 bmdykinin receptor gene[J].Hum Genet,1996,97:688-689
[22]王兵,刘过仗,党爱民.缓激肽p2受体基因启动区点突变与高血压病的关系[J]。中国心血管病杂志,2001,29(4):203-205
[23]Mukae S,Aoki s,Itoh SET AL.Promoter polymorphism of the beta2-bradykinin receptor gene is associated with essential hypertension[J].Jpn Cire J,1999,63(10):759-762.
[24]Gainer JY,Brown NJ,Bachvarova M et al.Altered frequency of a promoter polymorphism of the kinin β2 receptor gene in hypertensive African-American[J].Am J Hypertens,2000,13(12):1268-1273.
[25]汪迎春,李南方,周令。缓激肽β2受体启动子区SSCP带型与新疆哈萨克族人原发性高血压的相关性分析[J]。新疆医科大学学报,2005,28(1):12-14.
[26]Sugimoto K,Hozawa A,Katsuya T et al.α-Adducin Gly460Trp polymorphism is associated with low rennin hypertension in younger subjects in the ohasama study[J].Hypertens.2002,20(9),1779-1784.
[27]Kedzierska K,Ciechanowki K,Safranow K,et al.CNB3 C875T and ACEI/I) polymorphism on the sodium-proton etciznger and the prevalence of essential hypertension in nules[J].Arch MedRes,2006,37(1):150-157.
[28]Dong Y,Zhu H,Wang X et al.Obesity reveals an association between blood pressure and the G-protein beta3-subunit gene;a study of female dizygotic twins[J].Pharmacogeneties,2004,14(7):419-427.
[29]Danoviz ME,Pereira AC,Mill JG et al.Hypertension,obesity and GNB3 gene variants[J].Clin Exp Pharmacol Pharrnacol Physiol,2006,33(3):248-252.
[30]Shioji K,Kokubo Y Mannami T,et al.Association between hypertension and the α-adducin,betal-adrenoreceptor,and G-protein beta3 subunit genes in the Japanese population:the Suita study[J].Hypertens Res,2004:27(1):31-37.
[31]Yeomin Y.Junghan S.Seung Ho.et al.Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease[J].Clinical chemistry.2000.46:1626-1630.
[32]Makrina DS.Patrick JTV.Kypros HN et al.Hingorain endothelial nitric oxide synthase gene polymorphism and maternal vascular adapfion to,pregnancy[J].Hypertension.2001,38:1289.
[33]Naber CK Baumgart D.A ltmann C.et al.Enos 894T allele and coronary blood flow at rest and during adenosiner-induced hyperemia[J].Am J Physiol.(2001) 281.H 1908-1912.
[34]Hyndman ME.Parsons HG vermas.et al.The T-786→C mutation in endothelial nitric oxide synthase is associated with hypertension[J].2002,39(4):919-922.
[35]Marteau JB,Sass C.Pfister Met al.The Leu554 phe polymorphism in the E-selection gene is associated with blood pressure in overweight people[J].Hypertens,2004,22(2):305-311.
[36]陈海翎,华琦,刘荣坤。E-选择素A 561C(S128R)基因多态性对动脉血压的影响[J]。心肺血管病杂志,2005,24(4):196-200.
[37]Jin JJ,Nakura J,Wu ZH,et al.Association ofEndothelin-1 gene variant with hypertension[J].Hypertension.2003,41:163-167.
[38]Iwai N,Katsuya T,Ishikawa K,et al.Human prostacyclin synthase gene and hypertension[J].The Suita Study.Circulation,1999,100:2231-2236.
[39]岳月红,王慧凌,高阳。原发性高血压相关基因研究[J]。国外医学,老年医学分册。2007,28(4):165-169
[40]Yang W,Huang J,Ge D et al.Variation near the region of the lipprotein lipase gene and hypertension or blood pressure levelsin Chinese[J].Hypertension Res,2006,26(6):459-464
[41]邱长春,朱席琳,纪和荣。原发性高血压病胰岛素基因的分析[J]。中国医学科学院学报,1995,17(2):81-85.
[42]林从容,吴可桂,谢良地。胰岛素受体基因第8外显子NsI Ⅰ多态性与中国人高血压[J]。中华医学遗传学杂志,2000,17(5):364-365.
[43]Thomas GN,Tomlinson B,Chart JC et al.An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome[J].Am J Hypertens,2000,13(7):745-752.
[44]Pual J,Lijnen,Victor V,et al.Association Between Transforming Growth Factor-β and Hypertension[J],Hypertens,2003,16:604-611.
[45]林从容,吴可桂,谢良地。胰岛素受体基因第8外显子NsI Ⅰ多态性与中国人高血压[J]。中华医学遗传学杂志,2000,17(5):364-365.
[46]Richard P.Lifton.Genetic determinants of human hypertension[J].Proc.Natl.Aead.USA.Vol.92.pp:8545-8551,September 1995.
[47]LiB,Khanna A.Shamav,et al.TGF-β1 DNA polymorphism protein levels and blood pressure[J]Hypertension,1999,33:181-188.
[48]Yamada Y,Fujisawa M,Ando F,et al.Association ofa polymorphism of the transforming growth factor-j31 gene with blood pressure in Japanese individual[J].Genet.2002.47(5):243-248.
[49]Hamet P,Pausova Z,Adaricher V,et al,Hypertension;genes and environment[J].Hypertens,1998,16:397-418.
[2]王文鹃,王克安,李大麟,等.体质指数、腰围和腰臀比预测高血压、高血糖的实用价值及其建议值探讨[J].中华流行病学杂志,2002,23(1):16-19
[3]Shoji M,Tsutaya S,Satio R,etal.Positive association of endothelial nitric oxide synthase gene polymorphism with hypertension in northern Japan[J].Life Sci,2000.66:2557-2562.
[4]Miyamoto Y,Satio Y,Kajiyama N,etal.Endothelial nitric oxide sythase gene is positively associated with essential hypertension[J].Hypertension,1998,32:3-8.
[5]Kishimoto T,Misawa Y,Kaetu A,et al.eNOS Glu298Asp polymorphism and hypertension in a cohort study in Japanese[J].Preventive Medicine 39(2004) 927-931.
[6]Jeunematir X,Soubrier F,Kotelevtser Y,et al.Molecular basis of human hypertension:role of angiotensinogen[J].Cell,1992,71:169-180
[7]Sethi AA,Nordestgaard BG,Agerholm-Larsen B,et al.Angiotensinogen polymorphisms and elevated blood pressure in the general population:the Copenhagen city heart study[J].Hypertension,2001,37(1):875-881
[8]Sato N,Katsuya T,Nakagawa T,et al.Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension[J].Life Sci,2000(68):259-272
[9]Jeunemaitre X,Inoue I,Williams C,et al.Haplotypes ofangiotensinogen inessential hypertension[J].Am J Hum Genet,1997(60):1448-1460
[10]Hegele RA,Brunt JH,Connelly PW.Genetic and biochemical factors associated with variation in blood pressure in a genetic isolate[J].Hypertension,1996,27:308-312
[11]Formiguera X,Canto'n A.Obesity:epidemiology and clinical aspects[J].Best Practice &Research Clinical Gastroenterology.2004.Vol.18,No.6,pp:1125-1146.
[12]Carlos A.Feldstein,Maia Akopian,etal.A comparison of body mass index and waist-to-hip ratio as indicators of hypertension risk in an urban Argentine population:A hospital-based study[J].Nutrition,Metabolism & Cardiovascular Diseases(2005) 15,310-315.
[13]周和,陈思东,张信,等。中年知识分子体重指数、腰围及腰臀比与高血压发生的风险性分析[J]。广州医学院学报,2004,March,32(1):55-59,62。
[14]叶浩风,赵小兵,吴伟峰,等.农村居民高血压与体质指数、腰臀比关系的研究[J]。职业与健康,2005,21(9):1288.1290.
[15]石学香,逢增昌,汪韶洁,等.青岛市成人体质指数及其腰围与高血压的关系[J].中国慢性病预防与控制,2006,14(6):444-445。
[16]Ishigami T,Umemura S,Wamoto T,Tamura K,Hibi K,Yamaguchi S,etal.Molecular variant ofangiotensinogen(AGT) gene is associated with coronary atherosclerosis[J].Circulation,1995,91(4):951-954.
[17]贾崇奇,赵仲堂,王立华,等。一氧化氮合酶基因G894T变异与高血压病关系的研究[J]。中华流行病杂志,2003,24(1):677-680。
[18]Shoji M,Tsutaya S,Satio R,etal.Positive association of endothelial nitric oxide synthase gene polymorphism with hypertension in northern Japarl[J].Life Sci,2000.66:2557-2562.
[19]李东宝,华琦,皮林。内皮性一氧化氮合酶基因G894T多态性与与原发性高血压的相关关系[J]。高血压杂志,2004,Aug,12(4):326-330。
[20]张丽萍,汪师贞,赵学信,等。内皮型一氧化氮合酶基因G894T多态性与新疆维吾尔族原发性高血压的关联研究[J]。中华心血管病杂志,2006,May,34(5):403-406。
[21]王琳,陈丹,薛雨,等。内皮型一氧化氮合酶基因Glu298Asp多态性与原发性高血压的关系[J]。国际遗传学杂志,2006,Oct,29(5):336-340。
[22]Zhao Qi,Su Shao-yong,Chen Shu-feng.Association study of the endothelial nitric oxide synthasegene polymorphisms with essential hypertension in northern Han Chinese[J].Chinese Medical Journal 2006;119(13):1065-1071.
[23]Jeunemaitre X,Soubrier F,Kotelevtsev YV,et al.Molecular basis of human hypertension:Role ofangiotensinogen[J].Cell,1992,71(1):169-180.
[24]Yee-How Say,King-Hwa Ling,Gnanasothie Duraisamy.Angiotensinogen M235T gene variants and its association with essential hypertension and plasma renin activity in Malaysian subjects:A case control study[J].BMC Cardiovascular Disorders.2005,5:7.
[25]孙琦,柳青,雷寒。血管紧张素原M235T基因多态性与重庆地区原发性高血压的关系[J]。重庆医学,2002,November,31(11):1072-1073。
[26]蔡思宇,俞峰,施育平。血管紧张素原M235T基因多态性与原发性高血压的相关研究[J]。浙江大学学报(医学版),2004,33(2):151-154。
[27]Adrian Mondry,Marie Loh,Pengbo Liu,Ai-Ling Zhu.Polymorphisms of the insertion /deletion ACE and M235T AGT genes and hypertension:surprising new findings and meta-analysis of data[J].BMC Nephrology 2005,6:1.
[28]Wenquan NIU,Yue QI,Weijun CEN.Genetic Polymorphisms of Angiotensinogen and Essential Hypertension in a Tibetan Population[J].Hypertens Res Vol.30,No.11(2007):1129-1137
[29]BARBARA NEMESURE,SUH-YUH WU,ANSELM HENNIS.The Relationship of Body Mass Index and Waist-Hip Ratio on the 9-Year Incidence of Diabetes and Hypertension in a Predominantly African-origin Population[J].AEP Vol.18,No.8 August 2008:657-663
[30]Witteman JC,Willett WC,Stampfer MJ,etal.Aprospetive study of nutritiona 1 factors and hypertension among US women[J].Circulation,1989,80:1320-1327
[31]孙蓉,顾建建,孙峰。江苏省自然人群高血压患病率及相关因素分析[J]。江苏临床医学杂志,2002年第6(6):534-536
[32]王薇,吴兆苏,刘静,等。11省市自然人群原发性高血压患病率及相关因素的流行病学研究[J]。心脑血管病杂志,1998,17(2):81
[33]Kuschnir MC,Mendonca GA.Risk factors associated with arterial hypertension in adolescents[J].J Pediatr(Rio J).2007,83(4):335-342
[34]陈晓荣,汪韶洁,逢增昌,等.青岛市城乡部分中老年人肥胖现况调查[J]。预防医学文献息,2003,9(6):671-672
[35]周晓红,路方红,金世宽等。血管紧张素原M235T基因多态性及体重指数与原发性高血压的关系[J]。中国老年学杂志,2008,May,28(9):875-877
[1]Ismail M,Akhtar N,Nasir M,et al Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and essential hypertension in young Pakistani patients[J].Biochem Mol Biol,2004,37(5):552-5.
[2]巩云霞,庞小芬,朱理敏,等。ACE基因多态性与老年人原发性高血压的关系[J]。实用老年医学。2001,15(5):115-121.
[3]Markovic D,Tang X,Guruju M,et al.Association of angiotensinogen gene polymorphism with essential hypertension in African-Americans and Caucasians[J].Hum Hered,2005,60(2):89-96.
[4]Jain S,Li Y,Patil S,et al A single-nucleotide polymorphism in human angiotensinogen gene is associated with essential hypertension and affects glucocorticoid induced promoter activity[J].Mol Med,2005,83(2):121-131.
[5]Tsai CT,Falin D,Chiang FT,et al.Angiotensinogen gene haplotype and hypertension[J].Hypertens,2003,41:9215.
[6]Renner W,Nauck M,Winkelmann BR,et al.Assotiation of angiotensinogen haplotypes with angiotensinogen levels but not with blood pressure or coronary artery disease[J],the Ludwigshafen Ridk and Cardiovascular Heath Study.Mol,2005,83(3):235-239.
[7]Yanai K,Nibu Y,Murakami K et al.A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequencea in human angiontensinogen gene[J].J Biol Chem,1996,271(27):15981-15986.
[8]Brand Herrmann SM,Kopke K,Reichenberger F et al.Angiotensinogen promoter haplotypes are associated with blood pressure in untreated hypertensives[J].Hypertens,2004,22(7):1289-1292.
[9]Vasku A,Soucek M,Tahoplova S et al.An association of BMI with A(-6) G,M235T and T174M polymorphisms in angiotensinogen gene in essential hypertension[J].Hum Hypertens,2002,16(6):427-430.
[10]Frossard PM,Lestingany GG,Malloy MJ,et al.Human rennin gene dimorphism associated with hypertension in two independent populations[J].Clin Genet,1999,56(6):428.
[11]Asai,Masayoshi Soma,Shinichiro Kokubun et al.Haplotype Analysis of the human renin Gene and Essential Hypertension[J].Hypertension,2003,41:308-312.
[12]Chiang FT Hsu KL,Tseng CD,et al.Association of the rennin gene polymorphism with essential hypertension in a Chinese population[J].Clin Genet,1997,51(6):370.
[13]宋卫华 党爱民等。原发性高血压相关基因研究进展[J]。Molecular Cardiology of China, April 2005,Vol 5.No 2.Serial No 21.
[14]Henderson SO,Naiman CA,Mack W.Mutiple polymorphisms in the rennin-aldosterone system(ACE,CYP11B2,AGTR1 ) and their contribution to hypertension in African Americans and Lations in the multienthnic cohort.Am J Med Sci,2004,328(5):266-273.
[15]Kotanko P,Binder A,Tasher Jet al,Essential hypertension in African Caribbeans with a variants of the beta2-adrenoceptor[J].Hypertension,1997,30(4):773-776.
[16]Jindra A.Horkyk,Peleska Jet al.Association analysis of Arg 16 Gly polymorphism of the beta2-adrenergic receptor gene in offspring from hypertension and normotensive families[J].Blood press.2002,11(4):213-217.
[17]Herrmann SM,Nicaud V,Triet Let al.Polymorphisms of the beta2-adrenoceptor(ADRB2)gene and essential hypertension:the ECTIM and PEGASE Studies[J].Hypertension,2002,20(2):229-235.
[18]Tomaszewski M,Brain N J,charchar FJ et al.Essential hypertension and beta2-adrenergic receptor-gene;linkage and association[J].Hypertension.2002,40(3):286-291.
[19]Braun A,Maier S,Kammerer Set al.A novel sequence polymorphism in the promoter region of the human β2 bradykinin receptor gene[J].Hum Genet,1996,97:688,689.
[20]Tomaszewski M,Brain N J,Charchar FJ etal.Essential hypertension and beta2-adrenergic recetor gene;linkage and association[J].Hypertension,2002,40(3):286-291.
[21]Braun A,Maier S,Kammerer Set al.A novel sequence polymorphism in the promoter region of the human 132 bmdykinin receptor gene[J].Hum Genet,1996,97:688-689
[22]王兵,刘过仗,党爱民.缓激肽p2受体基因启动区点突变与高血压病的关系[J]。中国心血管病杂志,2001,29(4):203-205
[23]Mukae S,Aoki s,Itoh SET AL.Promoter polymorphism of the beta2-bradykinin receptor gene is associated with essential hypertension[J].Jpn Cire J,1999,63(10):759-762.
[24]Gainer JY,Brown NJ,Bachvarova M et al.Altered frequency of a promoter polymorphism of the kinin β2 receptor gene in hypertensive African-American[J].Am J Hypertens,2000,13(12):1268-1273.
[25]汪迎春,李南方,周令。缓激肽β2受体启动子区SSCP带型与新疆哈萨克族人原发性高血压的相关性分析[J]。新疆医科大学学报,2005,28(1):12-14.
[26]Sugimoto K,Hozawa A,Katsuya T et al.α-Adducin Gly460Trp polymorphism is associated with low rennin hypertension in younger subjects in the ohasama study[J].Hypertens.2002,20(9),1779-1784.
[27]Kedzierska K,Ciechanowki K,Safranow K,et al.CNB3 C875T and ACEI/I) polymorphism on the sodium-proton etciznger and the prevalence of essential hypertension in nules[J].Arch MedRes,2006,37(1):150-157.
[28]Dong Y,Zhu H,Wang X et al.Obesity reveals an association between blood pressure and the G-protein beta3-subunit gene;a study of female dizygotic twins[J].Pharmacogeneties,2004,14(7):419-427.
[29]Danoviz ME,Pereira AC,Mill JG et al.Hypertension,obesity and GNB3 gene variants[J].Clin Exp Pharmacol Pharrnacol Physiol,2006,33(3):248-252.
[30]Shioji K,Kokubo Y Mannami T,et al.Association between hypertension and the α-adducin,betal-adrenoreceptor,and G-protein beta3 subunit genes in the Japanese population:the Suita study[J].Hypertens Res,2004:27(1):31-37.
[31]Yeomin Y.Junghan S.Seung Ho.et al.Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease[J].Clinical chemistry.2000.46:1626-1630.
[32]Makrina DS.Patrick JTV.Kypros HN et al.Hingorain endothelial nitric oxide synthase gene polymorphism and maternal vascular adapfion to,pregnancy[J].Hypertension.2001,38:1289.
[33]Naber CK Baumgart D.A ltmann C.et al.Enos 894T allele and coronary blood flow at rest and during adenosiner-induced hyperemia[J].Am J Physiol.(2001) 281.H 1908-1912.
[34]Hyndman ME.Parsons HG vermas.et al.The T-786→C mutation in endothelial nitric oxide synthase is associated with hypertension[J].2002,39(4):919-922.
[35]Marteau JB,Sass C.Pfister Met al.The Leu554 phe polymorphism in the E-selection gene is associated with blood pressure in overweight people[J].Hypertens,2004,22(2):305-311.
[36]陈海翎,华琦,刘荣坤。E-选择素A 561C(S128R)基因多态性对动脉血压的影响[J]。心肺血管病杂志,2005,24(4):196-200.
[37]Jin JJ,Nakura J,Wu ZH,et al.Association ofEndothelin-1 gene variant with hypertension[J].Hypertension.2003,41:163-167.
[38]Iwai N,Katsuya T,Ishikawa K,et al.Human prostacyclin synthase gene and hypertension[J].The Suita Study.Circulation,1999,100:2231-2236.
[39]岳月红,王慧凌,高阳。原发性高血压相关基因研究[J]。国外医学,老年医学分册。2007,28(4):165-169
[40]Yang W,Huang J,Ge D et al.Variation near the region of the lipprotein lipase gene and hypertension or blood pressure levelsin Chinese[J].Hypertension Res,2006,26(6):459-464
[41]邱长春,朱席琳,纪和荣。原发性高血压病胰岛素基因的分析[J]。中国医学科学院学报,1995,17(2):81-85.
[42]林从容,吴可桂,谢良地。胰岛素受体基因第8外显子NsI Ⅰ多态性与中国人高血压[J]。中华医学遗传学杂志,2000,17(5):364-365.
[43]Thomas GN,Tomlinson B,Chart JC et al.An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome[J].Am J Hypertens,2000,13(7):745-752.
[44]Pual J,Lijnen,Victor V,et al.Association Between Transforming Growth Factor-β and Hypertension[J],Hypertens,2003,16:604-611.
[45]林从容,吴可桂,谢良地。胰岛素受体基因第8外显子NsI Ⅰ多态性与中国人高血压[J]。中华医学遗传学杂志,2000,17(5):364-365.
[46]Richard P.Lifton.Genetic determinants of human hypertension[J].Proc.Natl.Aead.USA.Vol.92.pp:8545-8551,September 1995.
[47]LiB,Khanna A.Shamav,et al.TGF-β1 DNA polymorphism protein levels and blood pressure[J]Hypertension,1999,33:181-188.
[48]Yamada Y,Fujisawa M,Ando F,et al.Association ofa polymorphism of the transforming growth factor-j31 gene with blood pressure in Japanese individual[J].Genet.2002.47(5):243-248.
[49]Hamet P,Pausova Z,Adaricher V,et al,Hypertension;genes and environment[J].Hypertens,1998,16:397-418.