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Association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance in clopidogrel-treated Chinese

Zhong Ling Zhuo, Hai Peng Xian, Yan Long

  • 1Department of Clinical Laboratory, Peking University People's Hospital; Beijing-China. zhaoxt@bjmu.edu.cn.

Anatolian Journal of Cardiology
|January 20, 2018
PubMed

Insights

Genetic variations in CYP2C19, specifically the *2 or *3 alleles, are linked to clopidogrel resistance in cardiovascular patients. ABCB1 gene variations did not show a significant association with clopidogrel resistance in this study.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Genetics

Background:

  • Clopidogrel is a widely used antiplatelet medication for cardiovascular disease.
  • Genetic polymorphisms can influence clopidogrel's efficacy, leading to variable patient responses.
  • Understanding these genetic associations is crucial for personalized antiplatelet therapy.

Purpose of the Study:

  • To investigate the association between specific genetic polymorphisms in CYP2C19 and ABCB1 genes and clopidogrel resistance (CR).
  • To evaluate the impact of these genetic variations on antiplatelet response in patients with cardiovascular disease in Beijing.

Main Methods:

  • A study involving 325 patients with cardiovascular disease, divided into experimental (n=101) and control (n=224) groups.
  • Clopidogrel resistance was determined by adenosine diphosphate (ADP)-induced platelet inhibition rate using thromboelastography (TEG).
  • Genotyping for CYP2C19 (*2, *3, *4, *5, *17) and ABCB1 polymorphisms was performed using time-of-flight mass spectrometry and Sanger sequencing.

Main Results:

  • Carriage of CYP2C19*2 or *3 mutant alleles was significantly associated with lower ADP-induced platelet inhibition rates and increased risk of clopidogrel resistance (p<0.05).
  • No significant correlation was found between ABCB1 genotypes and an increased risk of clopidogrel resistance.
  • CYP2C19 heterozygous and homozygous genotypes (*1/*2, *1/*3, *2/*2, *2/*3) showed significantly reduced platelet inhibition compared to non-carriers.

Conclusions:

  • The presence of CYP2C19*2 or *3 mutant alleles is a significant predictor of attenuated platelet response to clopidogrel and elevated clopidogrel resistance risk.
  • CYP2C19 genetic variations play a critical role in clopidogrel efficacy in cardiovascular patients.
  • ABCB1 gene polymorphisms were not found to be significantly associated with clopidogrel resistance in this patient cohort.
Abstract

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