细胞色素P450氧化酶基因多态性与氯吡格雷治疗冠心病效果的相关性

摘要

目的 探讨汉族冠状动脉粥样硬化性心脏病患者细胞色素P450氧化酶系统(CYP2C19)基因多态性与氯吡格雷药物临床疗效的关系. 方法 176例经皮冠状动脉介入治疗(PCI)术后,接受阿司匹林+氯吡格雷双联抗血小板治疗,运用PCR-RFLP方法进行CYP2C19*2,*3两种突变等位基因检测,根据等位基因功能缺失,分析CYP2C19不同代谢基因型与心血管终点事件的相关性. 结果 CYP2C19*2和*3的等位基因频率分别为34.38％和5.97％,慢代谢基因型(*2/*2,*2/*3,*3/*3)占14.20％.随访中11例患者急性冠脉综合征再发,1例出现脑梗死,4例患者出现支架内血栓,心血管终点事件的发生率为9.09％.慢代谢基因型组心血管终点事件的发生率为16.00％,与非慢代谢基因型组(7.95％)比较差异无统计学意义(x2=1.683,P=0.195).结论 中国汉族冠心病患者CYP2C19慢代谢基因型频率高于高加索人种,但心血管终点事件的发生率并无明显升高.%Objective To investigate the association between CYP2C19 polymorphisms and efficacy of clopidogrel in Chinese Han patients with coronary atherosclerotic heart disease.Methods A total of 176 Chinese Han patients who underwent percutaneous coronary intervention and were treated with dual antiplatelet therapy with aspirin and clopidogrel were enrolled.Polymorphisms of CYP2C19 * 2,* 3 were measured by PCR-restriction fragment length polymorphism (PCR RFLP).The correlation between the genetic variants and cardiovascular events was analyzed.Results In the 176 patients,the allele frequencies of CYP2C19 * 2 and * 3 were 34.38％ and 5.97％ respectively,the percent of patients with poor metabolizer genotypes (* 2/* 2,* 2/* 3,* 3/* 3) was 14.20％.Among the 176 patients,11 patients reoccured acute coronary syndrome,1 patient suffered from stroke,and 4 patients had stent thrombosis.The incidence of cardiovascular events was 9.09 ％.Thecumulative incidence of cardiovascular events had no significant differences between poor metabolizer genotype carriers and extensive and intermediate metabolizer genotype carriers (16.00％ vs.7.95％,x2 =1.683,P=0.195).Conclusions The frequencies of CYP2C19 poor metabolizer genotypes are higher in Chinese Han population than in Caucasians,but the incidence of cardiovascular events in Chinese Han population is not increased.