在基于人群的海因茨·尼克斯多夫召回研究中，GNB3基因825位点TT变异可预测严重冠状动脉事件。

GNB3 gene 825 TT variant predicts hard coronary events in the population-based Heinz Nixdorf Recall study.

作者信息

Frey Ulrich H, Moebus Susanne, Möhlenkamp Stefan, Kälsch Hagen, Bauer Marcus, Lehmann Nils, Nöthen Markus, Mühleisen Thomas W, Stang Andreas, Erbel Raimund, Jöckel Karl-Heinz, Peters Jürgen, Siffert Winfried

机构信息

Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.

Institut für medizinische Informatik, Biometrie und Epidemiologie, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.

出版信息

Atherosclerosis. 2014 Dec;237(2):437-42. doi: 10.1016/j.atherosclerosis.2014.08.025. Epub 2014 Aug 28.

DOI:10.1016/j.atherosclerosis.2014.08.025

PMID:25463071

Abstract

OBJECTIVE

The C825T polymorphism of the gene encoding the human G protein beta-3 subunit (GNB3) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level.

METHODS

In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45-75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders.

RESULTS

The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% (p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2-2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6-4.2; p < 0.001).

CONCLUSION

The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males.

摘要

目的

人类G蛋白β-3亚基（GNB3）编码基因的C825T多态性与高血压和肥胖相关。此外，GNB3多态性的基因型与冠状动脉疾病的发生有关，并且825T等位基因被认为会影响动脉粥样硬化进程。然而，在人群水平的纵向研究中，C825T多态性预测冠状动脉事件的潜力尚未得到充分探索。

方法

在海因茨·尼克斯多夫召回研究队列中的4159名白种人受试者（年龄：45 - 75岁，48%为男性）中，确定了GNB3 C825T多态性（rs5443）的基因型，并将其与致命和非致命性心肌梗死（严重冠状动脉事件）相关联。使用已确定的心血管危险因素来校正混杂因素。

结果

中位随访时间为9.9年（第1/3四分位数为9.5/10.2）。148名受试者（3.6%）发生了严重冠状动脉事件。10年无事件生存率为CC型96.1%；CT型96.9%，TT型93.7%（p = 0.018）。多变量分析显示，在对年龄、性别、糖尿病、收缩压、体重指数、高密度脂蛋白以及基线时电子束计算机断层扫描测定的冠状动脉钙化进行校正后，TT基因型是严重冠状动脉事件的显著危险因素（风险比（HR）= 1.9（95%置信区间（CI）1.2 - 2.9）；p = 0.008）。虽然女性的预后与GNB3基因型无关，但男性的分析结果显示，TT基因型与C等位基因相比，HR甚至升高至2.6（95% CI 1.6 - 4.2；p < 0.001）。