Effect of the CYP2C192 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

被引：66

作者：

Tang, Xiao-Fang ^{[1
,2
,3
]}

Wang, Jing ^{[1
,2
,3
]}

Zhang, Jia-Hui ^{[1
,2
,3
]}

Meng, Xian-Min ^{[2
,3
,4
]}

Xu, Bo ^{[1
,2
,3
]}

Qiao, Shu-Bin ^{[1
,2
,3
]}

Wu, Yong-Jian ^{[1
,2
,3
]}

Chen, Jue ^{[1
,2
,3
]}

Wu, Yuan ^{[1
,2
,3
]}

Chen, Ji-Lin ^{[1
,2
,3
]}

Gao, Run-Lin ^{[1
,2
,3
]}

Yuan, Jin-Qing ^{[1
,2
,3
]}

Yang, Yue-Jin ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Med Sci, Fuwai Hosp, Dept Cardiol, Beijing 100037, Peoples R China

[2] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Cardiovasc Inst, Beijing 100037, Peoples R China

[3] Peking Union Med Coll, Beijing 100037, Peoples R China

[4] Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Fuwai Hosp, Beijing 100037, Peoples R China

来源：

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY | 2013年 / 69卷 / 05期

基金：

中国国家自然科学基金;

关键词：

Clopidogrel; Polymorphisms; CYP2C19; ABCB1; PON1; Platelet reactivity; ASSOCIATION TASK-FORCE; STENT THROMBOSIS; ANTIPLATELET THERAPY; PLATELET REACTIVITY; GENETIC-VARIANTS; TREATED PATIENTS; NO ASSOCIATION; INCREASED RISK; PARAOXONASE-1; POLYMORPHISMS;

D O I：

10.1007/s00228-012-1446-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. 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. 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. 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.

引用

页码：1103 / 1112

页数：10

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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 CYP2C192 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