Effect of the CYP2C19*2 and *3 genotypes, ABCB1 C3435T and PON1 Q192R alleles on the pharmacodynamics and adverse clinical events of clopidogrel in Chinese people after percutaneous coronary intervention
Effect of the CYP2C19*2 and *3 genotypes, ABCB1 C3435T and PON1 Q192R alleles on the pharmacodynamics and adverse clinical events of clopidogrel in Chinese people after percutaneous coronary intervention
复制标题
CYP2C19*2和*3基因型、ABCB1 C3435T和PON1 Q192R等位基因对中国人经皮冠状动脉介入治疗后氯吡格雷药效学和临床不良事件的影响
DOI：
10.1007/s00228-012-1446-8
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发表时间：
2013-05-01
影响因子：
2.9
通讯作者：
Yang, Yue-Jin
中科院分区：
文献类型：
--
作者：
Tang, Xiao-Fang;Wang, Jing;Yang, Yue-Jin
目的：中国人携带细胞色素P450 2C19 （CYP2C19）功能缺失等位基因的频率高于白种人。在经皮冠状动脉介入治疗后的中国患者中，atp结合盒、B亚家族、成员1 （ABCB1）和对氧磷酶1 （PON1）变异对氯吡格雷治疗后血小板反应性和临床结果的影响尚未有报道。本研究的目的是探讨CYP2C19、ABCB1和PON1变异对这些患者氯吡格雷药效学和临床结果的影响。方法：670例经皮冠状动脉介入治疗患者入组单中心登记。通过血栓弹性成像评估氯吡格雷抗血小板作用，通过连接酶检测反应检测CYP2C19、ABCB1和PON1基因型。主要临床终点包括心血管死亡、非致死性心肌梗死、靶血管重建术和支架血栓形成。次要临床终点为心肌梗死出血溶栓。随访期为12个月。结果：CYP2C19功能缺失等位基因频率较高（57.3%）。氯吡格雷低反应和复合缺血事件的风险随着CYP2C19功能缺失等位基因数量的增加而增加。然而，在ABCB1和PON1基因型组中，氯吡格雷的药效学和临床结果没有显著差异；在CYP2C19、ABCB1和PON1基因型组中，出血无显著差异。结论：CYP2C19功能缺失等位基因对氯吡格雷的药效学和复合缺血事件具有基因剂量效应。这些患者的ABCB1和PON1基因型对氯吡格雷抗血小板效果和临床结局均无显著影响。
Purpose:Chinese people are more frequent carriers of cytochrome P450 2C19 (CYP2C19) loss-of-function alleles than Caucasians. The effect of the ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase 1 (PON1) variants on platelet reactivity and clinical outcomes of clopidogrel treatment has not yet been reported in Chinese patients after percutaneous coronary intervention. The aim of this study was to investigate the effect of the CYP2C19, ABCB1, and PON1 variants on clopidogrel pharmacodynamics and clinical outcomes in these patients.Methods:Six hundred and seventy patients after percutaneous coronary intervention were enrolled in a single-center registry. The antiplatelet effect of clopidogrel was assessed by thromboelastography, and the CYP2C19, ABCB1, and PON1 genotypes were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.Results:The frequency of the CYP2C19 loss-of-function alleles was relatively high (57.3 %). The risk of a low response to clopidogrel and composite ischemic events increased with the number of CYP2C19 loss-of-function alleles. However, there were not significant differences in clopidogrel pharmacodynamics and clinical outcomes across the ABCB1 and PON1 genotype groups; bleeding was not significantly different across the CYP2C19, ABCB1, and PON1 genotype groups.Conclusions:The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients.