细胞色素P450 2C19基因多态性与氯吡格雷抗血小板作用相关性的Meta分析
The Relation of Cytochrome P450 Polymorphism and Antiplatelet Efficiency of Clopidogrel: A Meta-Analysis
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摘要: 目的 利用Meta分析的方法评估氯吡格雷抗血小板作用的效果和细胞色素P450 2C19基因(CYP2C19)多态性之间的相关性。 方法 计算机检索中国知网、万方、维普、中国生物医学文献数据库、Cochrane 图书馆、SCI、EMBASE和PubMed数据库,并手工检索相关杂志,收集氯吡格雷使用患者CYP2C19 A/G位点多态性的基因频率和抗血小板效应的独立病例对照研究,提取有效的数据,用RevMan 5.0软件进行Meta分析。 结果 共纳入8个病例对照研究,包括1 538例GG基因型患者和4 413例GA或者AA患者。Meta分析结果表明: 使用氯吡格雷作为抗血小板药物的患者中,CYP2C19 突变型(GA或者AA) 携带者比野生型GG携带者的药物敏感性差比值比=0.23,95% 可信区间(0.13,0.40);血浆药物浓度前者远低于后者均数差=-17.38,95% 可信区间(-25.59,-9.16);血小板反应指数前者较后者明显降低均数差=12.87,95%可信区间(8.48,17.26);支架植入后血栓形成情况前者较后者有明显增加比值比=3.68,95%可信区间(2.17,6.24);血栓导致的死亡率前者也较后者增高比值比=3.68,95%可信区间(1.82,7.43);然而,对于心肌梗死的情况前者与后者之间无差异比值比=1.25,95%可信区间(0.96,1.63)。 结论 Meta分析结果表明,CYP2C19基因多态性与氯吡格雷药物反应作用之间存在着一定的相关性,且易导致由于血小板凝集而造成的患者死亡。Abstract: Objective To assess antiplatelet efficiency for patients with cytochrome P450 polymorphisms using Clopidogrel. Method A comprehensive electronic search was carried out and 8 independent studies with a maximum of 1 538 cases and 4 413 controls were analyzed using the Cochrane Collaboration’s RevMan 5.0 software. Results Eight studies met the included criteria. There were statistically significant differences between loss-of-function CYP2C19 (GA or AA) and wild genotype(GG) for the response status to Clopidogrel: the fixed effects odds ratio(OR) was 0.23 95% confidence interval(CI) 0.13 to 0.40; for the plasma concentration levels of Clopidogrel: the random effects MD was -17.38(95% CI -25.59 to -9.16); for the platelet reactivity index of Clopidogrel: the random effects MD was 12.87 95% CI 8.48 to 17.26; for the definite stent thrombosis: the fixed effects OR was 3.68 (95% CI 2.17 to 6.24); for death of patients: the fixed effects OR was 3.68 (95% CI 1.82 to 7.43); however, there were no statistically significant differences between GA or AA and GG for myocardial infarction (MI): the fixed effects OR was 1.25 95% CI 0.96 to 1.63. Conclusions The presence of the loss-of-function CYP2C19 is associated with low plasma concentration, response status and antiplatelet efficacy of Clopidogrel and indicators of efficacy except for MI in patients using clopidogrel as antiplatelet agent.