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目的:采用Meta分析方法评价P2Y12基因多态性与心脑血管病患者氯吡格雷疗效及发生氯吡格雷抵抗的相关性。方法:计算机检索MEDLINE、Embase、中国知网、中文生物医学文献数据库、万方数据库(时间为1995年1月~2016年12月),全面收集有关血小板膜受体P2Y12基因多态性与发生氯吡格雷抵抗相关性的队列研究,纳入研究的受试者均为服用氯吡格雷的心脑血管疾病患者,排除动物实验研究,并对可纳入的研究进行严格的方法学质量评价,采用RevMan 5.1软件进行Meta分析。结果:最终纳入10篇队列研究(英文3篇,中文7篇),共5 223名受试者。Meta分析结果显示,使用氯吡格雷的心脑血管病患者中,C34T位点T等位基因携带者与CC型相比,发生不良心血管事件的风险的差异无统计学意义(RR=0.95,95%CI:0.82~1.09,P=0.46);G52T位点T等位基因携带者发生不良心血管事件的风险高于GG型患者,差异有统计学意义(RR=1.99,95%CI:1.63~2.44,P<0.000 01)。C34T位点T等位基因携带者发生氯吡格雷抵抗的风险高于CC型患者,差异有统计学意义(RR=2.02,95%CI:1.37~2.96,P=0.000 4)。G52T位点T等位基因携带者发生氯吡格雷抵抗的风险高于GG型患者,差异有统计学意义(RR=1.56,95%CI:1.04~2.34,P=0.03)。i-T744c位点C等位基因携带者发生氯吡格雷抵抗的危险与C等位基因非携带者相当,差异无统计学意义(RR=0.99,95%CI:0.78~1.25,P=0.92)。结论:C34T位点T等位基因可能是发生氯吡格雷抵抗的危险因素,G52T位点T等位基因可能是不良心血管事件和发生氯吡格雷抵抗的危险因素,i-T744c位点C等位基因的存在不会增加发生氯吡格雷抵抗的风险。
Objective: To evaluate the relationship between P2Y12 gene polymorphisms and clopidogrel efficacy and clopidogrel resistance in patients with cardiovascular and cerebrovascular diseases by Meta-analysis. METHODS: MEDLINE, Embase, CNKI, Chinese Biomedical Literature Database and Wanfang Database (from January 1995 to December 2016) were searched by computer to comprehensively collect information about the relationship between P2Y12 gene polymorphism of platelet membrane receptor and the occurrence of chlorine In a cohort study of the relationship between antihypertensive and anti-clopidogrel resistance, all cohorts enrolled were clopidogrel-treated patients with cardiovascular and cerebrovascular diseases, excluding animal studies and rigorous methodological evaluation of the studies included. RevMan 5.1 Meta-analysis software. Results: Finally, 10 cohort studies (3 in English and 7 in Chinese) were included in the study. A total of 5 223 subjects were enrolled. Meta-analysis showed that among clopidogrel-treated patients with cardiovascular disease, there was no statistically significant difference in the risk of adverse cardiovascular events between subjects with C allele at C34T locus and CC genotype (RR = 0.95, 95% CI: 0.82-1.09, P = 0.46). The risk of adverse cardiovascular events in T allele of G52T locus was higher than that in GG patients (RR = 1.99, 95% CI: 1.63 ~ 2.44, P <0.000 01). The risk of clopidogrel resistance in carriers of T allele at C34T locus was higher than that in patients with CC loci (RR = 2.02, 95% CI: 1.37-2.96, P = 0.0004). The risk of clopidogrel resistance in the T allele of G52T locus was higher than that in GG patients (RR = 1.56, 95% CI: 1.04-2.34, P = 0.03). The risk of clopidogrel resistance in carriers of allele C at i-T744c was comparable to that of non-carriers of C allele (RR = 0.99, 95% CI: 0.78-1.25, P = 0.92) . CONCLUSION: T allele of C34T locus may be the risk factor of clopidogrel resistance. The T allele of G52T locus may be a risk factor for adverse cardiovascular events and clopidogrel resistance, such as i-T744c locus C The presence of a bit gene does not increase the risk of clopidogrel resistance.