Hiura Yumiko, Fukushima Yasue, Yuno Miyuki, Sawamura Hiromi, Kokubo Yoshihiro, Okamura Tomonori, Tomoike Hitonobu, Goto Yoichi, Nonogi Hiroshi, Takahashi Rie, Iwai Naoharu
Department of Epidemiology, Research Institute, National Cardiovascular Center, Suita, Japan.
Circ J. 2008 Aug;72(8):1213-7. doi: 10.1253/circj.72.1213.
Recent large-scale genome-wide association studies have identified several loci associated with the risk of coronary artery disease (CAD). The aim of the present study was to examine whether the previously reported CAD-associated single-nucleotide polymorphisms (SNPs) confer susceptibility to myocardial infarction (MI) in a study population of 2,475 controls and 589 cases of MI. The effect of the CAD-associated SNPs on cardiovascular risk factors in the control group was also investigated.
Significant associations were observed between 2 SNPs, rs1333049 on chromosome 9p21 and rs17465637 on chromosome 1q41, and MI, with odds ratios adjusted for age, sex, diabetes, hypertension and smoking habit of 1.47 (95% confidence interval (CI), 1.15-1.89; corrected p=0.006) and 1.45 (95%CI, 1.15-1.83; corrected p=0.006) for rs1333049 and rs17465637, respectively. None of the genotypes was associated with body mass index, plasma lipid profile, blood pressure, glucose, or hemoglobin A1c. The genotypes also had no effect on the marker of inflammation (C-reactive protein) or atherosclerosis (mean and maximum carotid intima-media thickness).
Although the underlying mechanisms are not clearly understood, the previously reported association between the 2 SNPs (rs1333049 and rs17465637) and MI was reproduced in this Japanese sample.
近期大规模全基因组关联研究已确定了几个与冠状动脉疾病（CAD）风险相关的基因座。本研究的目的是在一个包含2475名对照和589例心肌梗死（MI）病例的研究人群中，检验先前报道的与CAD相关的单核苷酸多态性（SNP）是否会增加MI易感性。同时还研究了与CAD相关的SNP对对照组心血管危险因素的影响。
观察到2个SNP，即9号染色体p21区域的rs1333049和1号染色体q41区域的rs17465637与MI之间存在显著关联，在校正年龄、性别、糖尿病、高血压和吸烟习惯后，rs1333049和rs17465637的比值比分别为1.47（95%置信区间（CI），1.15 - 1.89；校正p = 0.006）和1.45（95%CI，1.15 - 1.83；校正p = 0.006）。没有任何一种基因型与体重指数、血脂谱、血压、血糖或糖化血红蛋白相关。这些基因型对炎症标志物（C反应蛋白）或动脉粥样硬化（平均和最大颈动脉内膜中层厚度）也没有影响。
尽管潜在机制尚不清楚，但在这个日本样本中重现了先前报道的2个SNP（rs1333049和rs17465637）与MI之间的关联。
