中国服用氯吡格雷冠心病患者CYP2C19基因多态性与血小板聚集抑制率相关性研究的系统评价

Systematic Review of the Relationship Between CYP2C19 Gene Polymorphism and Platelet Aggregation Inhibition Rate in Chinese Patients Taking Clopidogrel for Coronary Artery Disease

关键词:  中国  冠心病  氯吡格雷  CYP2C19  血栓弹力图  血小板聚集抑制率  抵抗  系统评价

Key words:  Chinese  coronary artery disease  clopidogrel  CYP2C19  thromboelastography  platelet aggregation inhibition rate  resistance  systematic review

摘要:

目的 系统评价服用氯吡格雷的中国冠心病患者其CYP2C19基因多态性与血栓弹力图（thromboelastography，TEG）检测的血小板聚集抑制率之间的相关性。方法 检索英文数据库PubMed、Embase、Cochrane图书馆和中文数据库中国知网（CNKI）、维普期刊资源整合服务平台（CQVIP）、万方数据知识服务平台、中国生物医学文献库（CBM），获得服用氯吡格雷且同时行CYP2C19基因多态性和TEG检测的中国冠心病患者资料。采用RevMan 5.3软件对患者CYP2C19基因多态性和TEG检测的血小板聚集抑制率及氯吡格雷抵抗率进行meta分析。结果 最终纳入25篇文献共计4 967例患者。Meta分析显示，快代谢型患者的血小板聚集抑制率显著高于中间代谢型[MD=9.17，95% CI（3.68，14.65），P=0.001]和弱代谢型[MD=20.63，95% CI（11.32，29.94），P<0.000 1]，且中间代谢型显著高于弱代谢型[MD=11.63，95% CI（5.60，17.67），P=0.000 2]。与此同时，快代谢型患者氯吡格雷抵抗的发生风险显著低于中间代谢型[RR=0.60，95% CI（0.53，0.67），P<0.000 01]和弱代谢型[RR=0.36，95% CI（0.28，0.47），P<0.000 01]，且中间代谢型显著低于弱代谢型[RR=0.59，95% CI（0.48，0.73），P<0.000 01]。结论 服用氯吡格雷的中国冠心病患者其CYP2C19基因多态性与TEG检测的血小板聚集抑制率之间存在明显的相关性，但临床在制定决策时仍应结合患者具体病情对其CYP2C19基因型和（或）血小板聚集抑制率做出正确解读。

Abstract:

OBJECTIVE To systematically evaluate the correlation between CYP2C19 gene polymorphism and platelet aggregation inhibition rate detected by thromboelastography in Chinese patients taking clopidogrel for coronary artery disease. METHODS Databases of PubMed, Embase, Cochrane's Library, CNKI, CQVIP, Wanfang and CBM were systematically searched for Chinese patients taking clopidogrel and simultaneously with CYP2C19 gene polymorphism and detected by thromboelastography. Meta-analyses of CYP2C19 gene polymorphism and platelet inhibition rate and the rate of clopidogrel resistance were performed with RevMan 5.3. RESULTS Twenty-five articles involving 4 967 patients were included for meta-analyses. For the platelet aggregation inhibition rate, extensive metabolizer was significant higher than intermediate metabolizer[MD=9.17, 95%CI(3.68, 14.65), P=0.001] and poor metabolizer[MD=20.63, 95%CI(11.32, 29.94), P<0.000 1], and intermediate metabolizer was significant higher than poor metabolizer[MD=11.63, 95%CI(5.60, 17.67), P=0.000 2]. Meanwhile, for the rate of clopidogrel resistance, extensive metabolizer was significant lower than intermediate metabolizer[RR=0.60, 95%CI(0.53, 0.67), P<0.000 01] and poor metabolizer[RR=0.36, 95%CI(0.28, 0.47), P<0.000 01], and intermediate metabolizer was significant lower than poor metabolizer[RR=0.59, 95%CI(0.48, 0.73), P<0.000 01]. CONCLUSION Although there is a significant correlation between the CYP2C19 gene polymorphism and the platelet aggregation inhibition rate detected by thromboelastography in Chinese patients taking clopidogrel for coronary artery disease, clinicians shall make the right interpretation with the CYP2C19 gene polymorphism and(or) the platelet aggregation inhibition rate, and clinical decision shall be made in combination with patient's specific conditions.