[Influence of CYP2C19 gene polymorphisms on the efficacy of clopidogrel treatment for the prevention of ischemic stroke following coronary stent implantation]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017 Dec 10;34(6):839-843. doi: 10.3760/cma.j.issn.1003-9406.2017.06.012.
[Article in Chinese]

Abstract

Objective: To assess the association of CYP2C19 gene polymorphisms with the incidence of ischemic stroke among patients receiving clopidogrel therapy following coronary stenting for coronary artery disease.

Methods: Clinical data of patients receiving clopidogrel therapy after coronary stenting were retrospectively studied. For a case-control study, 137 patients with acute cerebral infarction and 122 non-stroke patients were selected. Based on the variants of the CYP2C19 gene detected by a DNA microarray assay, the patients were further divided into the wild-type group(CYP2C19*1/*1) and mutant group(defined by the presence of at least one loss-of-function allele, including CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3). The incidences of ischemic stroke in the two groups were compared through a chi-square analysis. The influence of CYP2C19 gene polymorphisms and clopidogrel therapy on the incidence of ischemic stroke was analyzed through multivariable logistic regression.

Results: A total of 259 patients were enrolled. The case and control groups showed no difference in terms of gender and age. There were 123 cases (47.5%) in the CYP2C19 wild-type group and 136 cases (52.5%) in the mutant group. The incidence of ischemic stroke of mutant group was significantly higher than that of wild-type group (59.9% vs. 44.3%, X2=6.398, P=0.042). Multivariate analysis revealed that loss-of-function polymorphisms of the CYP2C19 gene carried a 1.13 times greater risk for ischemic stroke compared to wild-type genotype (OR=2.13, 95%CI: 1.23-3.71).

Conclusion: The efficacy of clopidogrel for the prevention of ischemic stroke in post-coronary stent patients may be reduced by the insufficiency of the CYP2C19 gene. The dosage of clopidogrel therapy should be adjusted based on its polymorphisms.

MeSH terms

  • Brain Ischemia / prevention & control*
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics*
  • Genotype
  • Humans
  • Percutaneous Coronary Intervention / adverse effects*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Genetic*
  • Stents / adverse effects*
  • Stroke / prevention & control*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Ticlopidine