European Journal of Clinical Pharmacology

, Volume 69, Issue 5, pp 1103–1112

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

  • Xiao-Fang Tang
  • Jing Wang
  • Jia-Hui Zhang
  • Xian-Min Meng
  • Bo Xu
  • Shu-Bin Qiao
  • Yong-Jian Wu
  • Jue Chen
  • Yuan Wu
  • Ji-Lin Chen
  • Run-Lin Gao
  • Jin-Qing Yuan
  • Yue-Jin Yang
Pharmacogenetics

DOI: 10.1007/s00228-012-1446-8

Cite this article as:
Tang, XF., Wang, J., Zhang, JH. et al. Eur J Clin Pharmacol (2013) 69: 1103. doi:10.1007/s00228-012-1446-8

Abstract

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.

Keywords

Clopidogrel Polymorphisms CYP2C19 ABCB1 PON1 Platelet reactivity 

Supplementary material

228_2012_1446_MOESM1_ESM.doc (140 kb)
ESM 1(DOC 140 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Xiao-Fang Tang
    • 1
  • Jing Wang
    • 1
  • Jia-Hui Zhang
    • 1
  • Xian-Min Meng
    • 2
  • Bo Xu
    • 1
  • Shu-Bin Qiao
    • 1
  • Yong-Jian Wu
    • 1
  • Jue Chen
    • 1
  • Yuan Wu
    • 1
  • Ji-Lin Chen
    • 1
  • Run-Lin Gao
    • 1
  • Jin-Qing Yuan
    • 1
  • Yue-Jin Yang
    • 1
  1. 1.Department of Cardiology, Fuwai Hospital and Cardiovascular Institute, National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.State Key Laboratory of Cardiovascular Disease, Fuwai Hospital and Cardiovascular Institute, National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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