Association between polymorphisms in the renin-angiotensin-aldosterone system genes and essential hypertension in the Han Chinese population.

Association between polymorphisms in the renin-angiotensin-aldosterone system genes and essential hypertension in the Han Chinese population.
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DOI:
10.1371/journal.pone.0072701
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhang Y
Zhang Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ji L;Cai X;Zhang L;Fei L;Wang L;Su J;Lazar L;Xu J;Zhang Y

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肾素-血管紧张素-醛固酮系统(RAAS)是人体内最重要的内分泌血压控制机制,其编码成分的基因已成为研究高血压遗传基础的有力候选者。然而,以往的研究主要集中在限制性多态,因此我们在中国汉族人群中开展了一项病例对照研究,系统地探讨RAAS基因多态与原发性高血压的关系。根据严格的纳入和排除标准,招募了905名高血压患者和905名正常血压对照。从HapMap中检索RAAS基因内的全部41个标签SNP,并使用GenomeLab SNPstream基因分型系统进行基因分型。采用Logistic回归分析、多因素降维(MDR)、分层分析和交叉分析等方法对SNPs与非遗传因素之间的交互作用进行识别和表征。高血压组血清总胆固醇(TC)、甘油三酯(TG)、体重指数(BMI)显著高于对照组。在41个SNP中,AGT内的rs3789678和rs2493132、ACE内的rs4305、AGTR1内的rs275645、CYP11B2内的rs3802230和rs10086846与高血压相关。MDR分析表明,BMI和rs4305之间的相互作用增加了高血压的易感性。交叉分析和分层分析进一步表明,BMI的影响较大,rs4305的影响较小。这些新的发现表明,RAAS中的这些基因变异与非遗传因素一起,可能在决定中国汉族人高血压易感性方面发挥重要作用。
Renin-angiotensin-aldosterone system (RAAS) is the most important endocrine blood pressure control mechanism in our body, genes encoding components of this system have been strong candidates for the investigation of the genetic basis of hypertension. However, previous studies mainly focused on limited polymorphisms, thus we carried out a case-control study in the Han Chinese population to systemically investigate the association between polymorphisms in the RAAS genes and essential hypertension. 905 essential hypertensive cases and 905 normotensive controls were recruited based on stringent inclusion and exclusion criteria. All 41 tagSNPs within RAAS genes were retrieved from HapMap, and the genotyping was performed using the GenomeLab SNPstream Genotyping System. Logistic regression analysis, Multifactor dimensionality reduction (MDR), stratified analysis and crossover analysis were used to identify and characterize interactions among the SNPs and the non-genetic factors. Serum levels of total cholesterol (TC) and triglyceride (TG), and body mass index (BMI) were significantly higher in the hypertensive group than in the control group. Of 41 SNPs genotyped, rs3789678 and rs2493132 within AGT, rs4305 within ACE, rs275645 within AGTR1, rs3802230 and rs10086846 within CYP11B2 were shown to associate with hypertension. The MDR analysis demonstrated that the interaction between BMI and rs4305 increased the susceptibility to hypertension. Crossover analysis and stratified analysis further indicated that BMI has a major effect, and rs4305 has a minor effect. These novel findings indicated that together with non-genetic factors, these genetic variants in the RAAS may play an important role in determining an individual’s susceptibility to hypertension in the Han Chinese.
DOI: 10.1007/s11906-011-0241-8
发表时间: 2012-02
影响因子: 5.6
作者:
Basson J;Simino J;Rao DC
通讯作者: Rao DC
血管紧张素II类型1型受体多态性和对高血压的易感性:巨大的综述。
DOI: 10.1097/gim.0b013e3181809613
发表时间: 2008-08
期刊: Genetics in medicine : official journal of the American College of Medical Genetics
影响因子: --
作者:
Mottl AK;Shoham DA;North KE
通讯作者: North KE
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发表时间: 2011-09-11
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