Yoshida Tetsuro, Kato Kimihiko, Yokoi Kiyoshi, Oguri Mitsutoshi, Watanabe Sachiro, Metoki Norifumi, Yoshida Hidemi, Satoh Kei, Aoyagi Yukitoshi, Nozawa Yoshinori, Yamada Yoshiji
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
Int J Mol Med. 2009 Nov;24(5):701-9. doi: 10.3892/ijmm_00000282.
Hypertension and diabetes mellitus are important risk factors for myocardial infarction (MI). The purpose of the present study was to identify genetic variants that confer susceptibility to MI in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of MI in such individuals. The study population comprised 5,835 unrelated Japanese individuals, including 1,339 subjects with MI and 4,496 controls. The 150 polymorphisms were selected by genome-wide association studies of MI and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set. The genotypes for these polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that three different polymorphisms were significantly (P<0.005) associated with the prevalence of MI in individuals with or without hypertension or diabetes mellitus: the C --> T polymorphism of CLEC16A (rs9925481) in individuals without hypertension, the A --> G polymorphism of SEMA3F (rs12632110) in individuals without diabetes mellitus and the A --> G polymorphism of ALOX5 (rs7913948) in individuals without hypertension or diabetes mellitus. No polymorphism was significantly associated with MI in individuals with hypertension, in those with diabetes mellitus, or in those with both conditions. Stratification of subjects based on hypertension or diabetes mellitus may thus be important in order to achieve personalized prevention of MI with the use of genetic information.
高血压和糖尿病是心肌梗死（MI）的重要危险因素。本研究的目的是识别在有或无高血压或糖尿病的个体中赋予MI易感性的基因变异，从而有助于对此类个体进行MI的个性化预防。研究人群包括5835名无亲缘关系的日本个体，其中1339名MI患者和4496名对照。通过使用基因芯片人类映射500K阵列集对MI和缺血性中风进行全基因组关联研究，选择了150个多态性位点。这些多态性位点的基因型通过一种将聚合酶链反应和序列特异性寡核苷酸探针与悬浮阵列技术相结合的方法来确定。卡方检验、对协变量进行调整的多变量逻辑回归分析以及逐步向前选择程序显示，三种不同的多态性位点与有或无高血压或糖尿病的个体中MI的患病率显著相关（P<0.005）：在无高血压个体中CLEC16A的C→T多态性（rs9925481）、在无糖尿病个体中SEMA3F的A→G多态性（rs12632110）以及在无高血压或糖尿病个体中ALOX5的A→G多态性（rs7913948）。在有高血压的个体、有糖尿病的个体或同时患有这两种疾病的个体中，没有多态性位点与MI显著相关。因此，基于高血压或糖尿病对受试者进行分层对于利用遗传信息实现MI的个性化预防可能很重要。
