日本人群中候选基因多态性所决定的心肌梗死遗传风险

Genetic risk for myocardial infarction determined by polymorphisms of candidate genes in a Japanese population.

作者信息

Yamada Y, Kato K, Oguri M, Fujimaki T, Yokoi K, Matsuo H, Watanabe S, Metoki N, Yoshida H, Satoh K, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y

机构信息

Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan.

出版信息

J Med Genet. 2008 Apr;45(4):216-21. doi: 10.1136/jmg.2007.054387. Epub 2007 Dec 12.

DOI:10.1136/jmg.2007.054387

PMID:18077766

Abstract

BACKGROUND

Although several environmental factors influence the development of myocardial infarction (MI), genetic factors have been shown to contribute to individual susceptibility to this condition.

OBJECTIVE

To identify gene polymorphisms that confer susceptibility to MI in order to allow assessment of genetic risk for this condition.

METHODS

3433 unrelated Japanese people (1931 men, 1502 women) were entered into the study. These comprised 1328 subjects with MI (1036 men, 292 women) and 2105 controls (895 men, 1210 women). The genotypes for 40 polymorphisms of 31 candidate genes were determined with a method that combines PCR and sequence-specific oligonucleotide probes with suspension array technology.

RESULTS

The chi(2) test revealed that six polymorphisms were significantly (false discovery rate <0.05) related to the prevalence of MI. Further examination by multivariable logistic regression analysis with adjustment for age, sex, body mass index and the prevalence of hypertension, diabetes mellitus and hypercholesterolaemia, in addition to a stepwise forward selection procedure found that the A-->C (Gln1334His) polymorphism (rs3742207) of the collagen type IV alpha-1 gene (COL4A1) and the A-->G polymorphism (rs4804611) of the zinc finger protein 627 gene (ZNF627) were significantly (p<0.05) associated with the prevalence of MI. The variant C allele of COL4A1 was protective against MI, whereas the variant G allele of ZNF627 represented a risk factor for this condition.

CONCLUSIONS

Determination of genotypes for COL4A1 and ZNF627 may prove informative for assessment of the genetic risk for MI.

摘要

背景

尽管多种环境因素会影响心肌梗死（MI）的发生发展，但遗传因素已被证明与个体对该疾病的易感性有关。

目的

确定赋予MI易感性的基因多态性，以便评估该疾病的遗传风险。

方法

3433名无亲缘关系的日本人（1931名男性，1502名女性）参与了这项研究。其中包括1328名MI患者（1036名男性，292名女性）和2105名对照者（895名男性，1210名女性）。采用聚合酶链反应（PCR）与序列特异性寡核苷酸探针相结合的悬浮阵列技术，对31个候选基因的40个多态性位点进行基因分型。

结果

卡方检验显示，六个多态性位点与MI的患病率显著相关（错误发现率<0.05）。除了逐步向前选择程序外，通过多变量逻辑回归分析进一步检查，并对年龄、性别、体重指数以及高血压、糖尿病和高胆固醇血症的患病率进行调整，发现IV型胶原α-1基因（COL4A1）的A→C（Gln1334His）多态性（rs3742207）和锌指蛋白627基因（ZNF627）的A→G多态性（rs4804611）与MI的患病率显著相关（p<0.05）。COL4A1的变异C等位基因对MI具有保护作用，而ZNF627的变异G等位基因是该疾病的一个危险因素。