Wong Cindy W, Christen Thomas, Pfenniger Anna, James Richard W, Kwak Brenda R
Foundation for Medical Research, Division of Cardiology, Department of Internal Medicine, Geneva University Hospitals, 64 Avenue de la Roseraie, 1211 Geneva 4, Switzerland.
Atherosclerosis. 2007 Apr;191(2):355-61. doi: 10.1016/j.atherosclerosis.2006.03.031. Epub 2006 May 4.
A C1019T polymorphism in the human connexin37 (hCx37) gene has been associated with cardiovascular risk, but it remains debatable whether the 1019C or the 1019T allele carries this risk. Here, we investigated whether these allelic variants are differentially predictive of increased risk for coronary artery disease (CAD) and myocardial infarction (MI). A total of 781 Swiss participants, including 597 patients diagnosed with CAD, 50% who reported previous MI, and 184 control subjects were genotyped. Patients in the +CAD group had a higher frequency of the Cx37-1019C allele (70.3% versus 65.0%, p=0.004). Multivariate analysis showed that the hCx37-C1019T polymorphism is an independent predictor of CAD (odds ratio=2.13, confidence interval=1.31-3.46 and p<0.01). Moreover, this polymorphism is not associated with any of the other characteristics examined, including gender, age, body-mass-index, diabetes, total/HDL/LDL-cholesterol, triglycerides, apoA-I, apoB, hypertension and cigarette smoking. In comparison with the -CAD group, we observed an increase of the Cx37-1019C allele in the +MI +CAD subgroup (71.2% versus 65.0%, p=0.002) but not in the -MI +CAD subgroup. Allelic frequency comparisons of these three subgroups predicted that this polymorphism is also an independent risk factor for MI. In conclusion, our results reveal the importance of screening the Cx37-1019C allele for both CAD and MI risk assessments.
人类连接蛋白37(hCx37)基因中的C1019T多态性与心血管风险相关,但携带这种风险的是1019C等位基因还是1019T等位基因仍存在争议。在此,我们研究了这些等位基因变异是否对冠状动脉疾病(CAD)和心肌梗死(MI)风险增加具有不同的预测作用。对总共781名瑞士参与者进行了基因分型,其中包括597名被诊断为CAD的患者,50%的患者报告有既往MI,以及184名对照受试者。CAD阳性组患者中Cx37 - 1019C等位基因的频率更高(70.3%对65.0%,p = 0.004)。多变量分析表明,hCx37 - C1019T多态性是CAD的独立预测因子(优势比 = 2.13,置信区间 = 1.31 - 3.46,p < 0.01)。此外,这种多态性与所检查的任何其他特征均无关联,包括性别、年龄、体重指数、糖尿病、总胆固醇/高密度脂蛋白/低密度脂蛋白胆固醇、甘油三酯、载脂蛋白A - I、载脂蛋白B、高血压和吸烟。与CAD阴性组相比,我们在MI阳性 + CAD亚组中观察到Cx37 - 1019C等位基因增加(71.2%对65.0%,p = 0.002),但在MI阴性 + CAD亚组中未观察到。这三个亚组的等位基因频率比较预测,这种多态性也是MI的独立危险因素。总之,我们的结果揭示了筛查Cx37 - 1019C等位基因对CAD和MI风险评估的重要性。