中国人群中血压与三个候选基因的关系。

Blood pressure in relation to three candidate genes in a Chinese population.

作者信息

Wang Ji-Guang, Liu Lifang, Zagato Laura, Xie Jinxiang, Fagard Robert, Jin Kugen, Wang Jinxiang, Li Yan, Bianchi Giuseppe, Staessen Jan A, Liu Lisheng

机构信息

Hypertension Division, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

J Hypertens. 2004 May;22(5):937-44. doi: 10.1097/00004872-200405000-00015.

DOI:10.1097/00004872-200405000-00015

PMID:15097233

Abstract

OBJECTIVE

In a prospective analysis of a Caucasian population, we recently found that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), alpha-adducin (Gly460Trp) and aldosterone synthase (-344C/T) jointly influence the incidence of hypertension. We therefore investigated the association between blood pressure and these three genes in a Chinese population.

METHODS

We genotyped 479 Han Chinese from 125 nuclear families recruited in northern China via random sampling (approximately 75%) and at specialized hypertension clinics (approximately 25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and the quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables.

RESULTS

The participants included 239 (49.9%) women and 132 (27.6%) hypertensive patients, of whom 77 took antihypertensive drugs. The blood pressure, measured at the subjects' homes, averaged 126/80 mmHg. Mean values of urinary sodium, potassium and Na/K ratio were 226 mmol/day, 37 mmol/day and 6.31, respectively. In adjusted GEE analyses, systolic blood pressure was 9.3 mmHg (95% confidence interval 3.6-15.0 mmHg; P = 0.001) and 14.6 mmHg (95% confidence interval 3.4-25.8 mmHg; P = 0.01) higher in the ACE DD than II subjects among the alpha-adducin TrpTrp (n = 141) and aldosterone synthase CC (n = 33) homozygotes, respectively (P < or =0.05 for interactions of the ACE genotype with the alpha-adducin and aldosterone synthase polymorphisms). Among 40 informative offspring homozygous for the alpha-adducin Trp allele, systolic blood pressure was significantly associated with transmission of the ACE D allele (beta = 5.5 mmHg; P = 0.046).

CONCLUSIONS

The ACE I/D, alpha-adducin Gly460Trp and aldosterone synthase -344C/T polymorphisms interact to influence systolic blood pressure in Chinese, suggesting that these genes might indeed predispose to hypertension, especially in an ecogenetic context characterized by a high salt intake.

摘要

目的

在一项针对高加索人群的前瞻性分析中，我们最近发现，编码血管紧张素转换酶（ACE，I/D多态性）、α-内收蛋白（Gly460Trp）和醛固酮合酶（-344C/T）的基因共同影响高血压的发病率。因此，我们在中国人群中研究了血压与这三个基因之间的关联。

方法

我们对通过随机抽样（约75%）和在专门的高血压诊所（约25%）招募的来自中国北方125个核心家庭的479名汉族人进行了基因分型。我们分别使用广义估计方程（GEE）和定量传递不平衡检验（QTDT）进行基于人群和基于家庭的关联分析，同时控制协变量。

结果

参与者包括239名（49.9%）女性和132名（27.6%）高血压患者，其中77人服用降压药。在受试者家中测量的血压平均为126/80 mmHg。尿钠、钾和钠/钾比值的平均值分别为226 mmol/天、37 mmol/天和6.31。在调整后的GEE分析中，在α-内收蛋白TrpTrp（n = 141）和醛固酮合酶CC（n = 33）纯合子中，ACE DD受试者的收缩压分别比II受试者高9.3 mmHg（95%置信区间3.6 - 15.0 mmHg；P = 0.001）和14.6 mmHg（95%置信区间3.4 - 25.8 mmHg；P = 0.01）（ACE基因型与α-内收蛋白和醛固酮合酶多态性的相互作用P≤0.05）。在40名α-内收蛋白Trp等位基因纯合的信息丰富的后代中，收缩压与ACE D等位基因的传递显著相关（β = 5.5 mmHg；P = 0.046）。