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Diversity of platelet function and genetic polymorphism in clopidogrel-treated Chinese patients

B Sun1, J Li2, M Dong1

  • 1Clinical Laboratory, The 309th Hospital of People's Liberation Army, Beijing, China.

Genetics and Molecular Research : GMR
|March 3, 2015
PubMed

Insights

Genetic variations in CYP3A5*3 and CYP2C19*2 impact clopidogrel effectiveness in coronary disease patients. These genetic polymorphisms are linked to higher risks of ischemia event relapse after stenting.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Chemistry

Background:

  • Clopidogrel is a widely used antiplatelet medication for patients undergoing percutaneous coronary intervention (PCI).
  • Individual variability in clopidogrel response can lead to suboptimal treatment outcomes, including ischemia event relapse.
  • Genetic polymorphisms in drug-metabolizing enzymes and receptors are implicated in altered drug efficacy.

Purpose of the Study:

  • To investigate the correlation between genetic polymorphisms of cytochrome P450 enzyme genes and clopidogrel treatment outcomes in coronary disease patients post-PCI.
  • To identify specific genetic markers associated with the risk of ischemia event relapse within six months of PCI.

Main Methods:

  • A cohort of 118 coronary disease patients undergoing PCI was studied.
  • Patients were categorized into ischemia event relapse group (IERG) and non-IERG (NIERG).
  • Platelet inhibition ratios were measured using thromboelastogram platelet mapping, and genotypes for CYP3A5*3, CYP2C19*2, and P2Y12*1 were analyzed.

Main Results:

  • Ischemia event relapse occurred in 26.27% of patients.
  • The ADP-induced platelet inhibition ratio was significantly lower in the IERG compared to the NIERG.
  • Mutant alleles CYP3A5*3 and CYP2C19*2 were associated with lower platelet inhibition and a higher frequency of ischemia event relapse, unlike P2Y12*1.

Conclusions:

  • Coexisting polymorphisms in CYP3A5*3 and CYP2C19*2 significantly influence clopidogrel's antiplatelet effect and are associated with increased risk of ischemia event relapse post-PCI.
  • P2Y12*1 genotype did not show a significant association with clopidogrel response or ischemia event relapse in this cohort.
  • These findings highlight the importance of pharmacogenetic testing for optimizing clopidogrel therapy in coronary artery disease patients.

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