日本代谢综合征患者基因变异与心肌梗死的关联

Association of genetic variants with myocardial infarction in Japanese individuals with metabolic syndrome.

作者信息

Oguri Mitsutoshi, Kato Kimihiko, Yokoi Kiyoshi, Itoh Tatsuo, Yoshida Tetsuro, Watanabe Sachiro, Metoki Norifumi, Yoshida Hidemi, Satoh Kei, Aoyagi Yukitoshi, Nishigaki Yutaka, Tanaka Masashi, Nozawa Yoshinori, Yamada Yoshiji

机构信息

Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.

出版信息

Atherosclerosis. 2009 Oct;206(2):486-93. doi: 10.1016/j.atherosclerosis.2009.02.037. Epub 2009 Mar 19.

DOI:10.1016/j.atherosclerosis.2009.02.037

PMID:19361803

Abstract

OBJECTIVE

The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in individuals with metabolic syndrome (MetS).

METHODS

The study population comprised 1887 Japanese individuals with MetS, including 773 subjects with MI and 1114 controls. The genotypes for 136 polymorphisms of 97 candidate genes were determined.

RESULTS

An initial screen by the chi-square test revealed that seven polymorphisms were significantly (false discovery rate<0.05) associated with the prevalence of MI in individuals with MetS. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the G-->A (Ser89Asn) polymorphism of UTS2 [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.18-3.08], the 2445G-->A (Ala54Thr) polymorphism of FABP2 (OR, 1.72; 95% CI, 1.23-2.40), the -11377C-->G polymorphism of ADIPOQ (OR, 1.43; 95% CI, 1.15-1.79), the -231A-->G polymorphism of EDNRA (OR, 0.65; 95% CI, 0.48-0.89), and the -108/3G-->4G polymorphism of PDX1 (OR, 0.64; 95% CI, 0.48-0.87) were significantly (P<0.05) associated with MI. The variant alleles of UTS2, FABP2, and ADIPOQ were risk factors for MI, whereas the variant alleles of EDNRA and PDX1 were protective against this condition. A stepwise forward selection procedure demonstrated that UTS2, FABP2, ADIPOQ, EDNRA, and PDX1 genotypes were significant (P<0.05) and independent determinants of MI.

CONCLUSIONS

Determination of genotypes for these polymorphisms of UTS2, FABP2, ADIPOQ, EDNRA, and PDX1 may prove informative for assessment of the genetic risk for MI in Japanese individuals with MetS.

摘要

目的

本研究旨在确定代谢综合征（MetS）个体中易患心肌梗死（MI）的基因变异。

方法

研究人群包括1887名患有MetS的日本个体，其中773名患有MI，1114名作为对照。测定了97个候选基因的136个多态性位点的基因型。

结果

通过卡方检验进行的初步筛选显示，7个多态性位点与MetS个体中MI的患病率显著相关（错误发现率<0.05）。随后进行的多变量逻辑回归分析并对协变量进行调整后发现，UTS2的G→A（Ser89Asn）多态性[比值比（OR），1.90；95%置信区间（CI），1.18 - 3.08]、FABP2的2445G→A（Ala54Thr）多态性（OR，1.72；95% CI，1.23 - 2.40）、ADIPOQ的 - 11377C→G多态性（OR，1.43；95% CI，1.15 - 1.79）、EDNRA的 - 231A→G多态性（OR，0.65；95% CI，0.48 - 0.89）以及PDX1的 - 108/3G→4G多态性（OR，0.64；95% CI，0.48 - 0.87）与MI显著相关（P<0.05）。UTS2、FABP2和ADIPOQ的变异等位基因是MI的危险因素，而EDNRA和PDX1的变异等位基因对MI有保护作用。逐步向前选择程序表明，UTS2、FABP2、ADIPOQ、EDNRA和PDX1的基因型是MI的显著（P<0.05）且独立的决定因素。