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

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。

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.