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首页> 外文期刊>The American Journal of Cardiology >Meta-analysis of cytochrome P450 2C19 polymorphism and risk of adverse clinical outcomes among coronary artery disease patients of different ethnic groups treated with clopidogrel
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Meta-analysis of cytochrome P450 2C19 polymorphism and risk of adverse clinical outcomes among coronary artery disease patients of different ethnic groups treated with clopidogrel

机译：氯吡格雷治疗不同族裔冠心病患者细胞色素P450 2C19基因多态性的Meta分析和不良临床结局的风险

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摘要

Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying <1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of <1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.
机译：假设细胞色素P450 2C19（CYP2C19）的功能丧失（LOF）变异与氯吡格雷治疗的冠状动脉疾病患者的血小板抑制程度降低和复发性缺血事件的风险增加有关;但是，西方国家的研究却得出了不同的结果。我们旨在评估CYP2C19 LOF变体对不同种族的临床结局的影响。这项荟萃分析包括16项前瞻性队列研究，包括7,035例携带<1 CYP2C19 LOF等位基因的患者和13,750例具有野生型基因型的患者。与氯吡格雷治疗期间的非携带者相比，<1 CYP2C19 LOF等位基因携带者的不良临床事件风险显着更高（几率[OR]为1.42，95％置信区间[CI]为1.13至1.78）。摘要OR显示CYP2C19 LOF变异与心脏死亡风险增加（OR 2.18，95％CI 1.37至3.47），心肌梗塞（OR 1.42，95％CI 1.12至1.81）和支架血栓形成（OR 2.41）之间存在显着相关性，95％CI 1.76至3.30）。按研究人群的种族进行的分层分析表明，与西方人群相比，亚洲人群中CYP2C19 LOF变异（OR 1.89,95％CI 1.32至2.72）的亚洲人群发生不良临床事件的可能性更高（OR 1.28,95％CI 1.00至1.64）。总之，LOF CYP2C19的携带者状态与接受氯吡格雷治疗的冠心病患者发生不良临床事件的风险增加相关，尽管根据种族在临床意义上存在差异。

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