CYP2C19基因多态性与氯吡格雷相关不良反应的Meta分析

Association between CYP2C19 polymorphism and Clopidogrel-induced adverse events: a Meta-analysis

目的系统性评价细胞色素P450同工酶中超家族CYP2C19酶基因多态性与氯吡格雷不良反应发生的相关性。方法计算机检索Pub Med、Science direct、Wiley online library、Web of Science、中国知网、万方数据库和维普中文科技期刊数据库,纳入CYP2C19基因多态性与氯吡格雷不良反应相关的研究,同时查阅检索结果中所附相似文献及参考文献,检索文献均为建库至2015年1月18日。由两名评价员单独进行文献筛选及资料提取,采用Rev Man 5.0软件进行Meta分析及计算合并OR值和95%CI。结果共纳入CYP2C19基因多态性与氯吡格雷不良反应相关文献18篇,突变基因型患者6165例,野生型患者13 055例。Meta分析结果显示,突变基因型患者氯吡格雷相关不良反应发生率显著高于野生型患者（OR=1.53,95%CI：1.19-1.97,P=0.0010）;亚组分析结果表明,亚洲人种中突变基因型患者氯吡格雷相关不良反应发生率显著高于野生型患者（OR=2.49,95%CI：1.96-3.16,P〈0.000 01）,而欧洲人群不存在这一现象（OR=1.26,95%CI：0.96-1.65,P=0.10）;心肌梗死Meta分析中,突变型患者明显高于野生型患者（OR=1.69,95%CI：1.37-2.08,P〈0.000 01）;突变型患者出现支架血栓的风险也显著高于野生型患者（OR=2.13,95%CI：1.68-2.70,P〈0.000 01）。结论 CYP2C19基因多态性与氯吡格雷治疗相关不良反应之间存在显著的相关性,CYP2C19基因多态性能增加氯吡格雷引发的副作用。

Objective To investigate the association between CYP2C19 gene polymorphism and Clopidogrel-related adverse events in patients by Meta-analysis. Methods The computer was used to retrieve articles from the Pub Med, Science direct, Wiley online library, Web of Science, CNKI, Wanfang database and VIP. The studies were searched and sorted out which studied the association between CYP2C19 gene polymorphism with Clopidogrel-induced adverse events, also combined with manually retrieving the references and similar results in the attached documents. The range of searching time was all from inception to January 18, 2015. Literature screening and data extracting were handled by two reviews independently. Rev Man 5.0 software was used to conduct the Meta-analysis and assessed the pooled OR and 95%CI. Results 18 articles about CYP2C19 gene polymorphism and Clopidogrel-related adverse events were enrolled. It showed that the total number of patients with variant gene was 6165, and the total number of patient with wild-type gene was 13 055. While the results showed that the risk of Clopidogrel-induced adverse events was strongly higher in patients with variant gene compared to wild-type patients（OR = 1.53, 95%CI： 1.19-1.97, P = 0.0010）. The further regional subgroup analysis showed that the occurrence of Clopidogrel-induced toxicity in Asian patients carrying mutation gene was significantly increased when compared to wild-type patients（OR = 2.49, 95%CI： 1.96-3.16, P〈0.000 01）, but not in European（OR = 1.26, 95%CI： 0.96-1.65, P = 0.10）. What＇s more, the risk of Clopidogrel-induced toxicity in variant patients was apparently increased when compared to wild-type patients in myocardial infarction（OR = 1.69, 95%CI： 1.37-2.08, P〈0.000 01） and stent thrombosis（OR = 2.13, 95%CI： 1.68-2.70, P〈0.000 01）Meta analysis. Conclusion The association between CYP2C19 polymorphism and Clopidogrel-induced adverse events is significant in our study. CYP2C19 polymorphism can increase the Clopidogrel-induced adverse reactions.