ABCB1、CYP3A5和PON1基因多态性对氯吡格雷临床疗效的影响  

Effect of the polymorphisms of ABCB1,CYP3A5 and PON1 genes on the clinical efficacy of clopidogrel

作　　者：雷晓辉[1,2] 翟娅婧 贺海蓉 王学良[3] 吕军[1] 

机构地区：[1]西安交通大学第一附属医院临床研究中心,陕西西安710061 [2]西安交通大学第二附属医院康复医学科,陕西西安710004 [3]西安交通大学医学部公共卫生学院,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2016年第5期726-733,共8页Journal of Xi’an Jiaotong University（Medical Sciences）

摘　　要：目的采用Meta分析方法评价冠心病患者肠道多药耐药蛋白1基因ABCB1、细胞色素P450基因CYP3A5、对氧磷酶-1基因PON1多态性与氯吡格雷疗效的关系。方法计算机检索PubMed及中国知网数据库到2015年3月6日为止的中英文相关文献。采用Stata 12.0软件进行Meta分析。结果共纳入35项研究,共32 675例患者。分别有19项和8项研究报道了ABCB1C3435T、CYP3A5 A6986G与氯吡格雷疗效的关系。Meta分析结果显示,ABCB1C3435T和CYP3A5A6986G多态性对患者主要心血管不良事件(MACE)的发生没有影响(OR=1.099,95%CI0.913,1.323,P=0.319;OR=0.844,95%CI0.784,1.220,P=0.844)。有19项关于PON1多态性的研究,发现Q192R突变与MACE的发生风险有关(OR=0.812,95%CI 0.671,0.984,P=0.033),但敏感性分析结果显示缺乏稳定性。结论 PON1Q192R突变可作为冠心病患者接受氯吡格雷治疗后不良心血管事件发生的危险因素,但需要更多高质量的研究证实。Objective To investigate the relationship of the polymorphisms of ABCB1,CYP3A5 and PON1 with clopidogrel response in patients with coronary heart disease.Methods We searched the PubMed and CNKI databases for related studies published up to March6,2015.Stata 12.0software was employed to perform the Metaanalysis.Results A total of 35 studies involving 32 675 patients were analyzed.Nineteen and eight researches reported the correlation of ABCB1 C3435 T and CYP3A5 A6986 G with clopidogrel response,respectively,but no correlation was found（OR=1.099,95% CI 0.913,1.323,P=0.319;OR=0.844,95% CI 0.784,1.220,P=0.844）.Nineteen studies examined PON1 polymorphisms,and Q192 R mutation was found to be related to the risk of major adverse cardiovascular events（OR=0.812,95% CI 0.671,0.984,P=0.033）.However,the result of sensitivity analysis showed lack of robustness.Conclusion PON1 Q192 R mutation is a risk factor for MACE in patients treated with clopidogrel.Future large-scale studies that include long-term follow-ups are still needed.

关 键 词：氯吡格雷 基因多态性 ABCB1 CYP3A5 PON1 META分析 

分 类 号：R574.62[医药卫生—消化系统]