Relationship of CYP2C19*2 and CYP2C19*3 Gene Polymorphism with Clopidogrel Response Variability and Recurrent Cardiovascular Events in Chinese Patients Undergoing Percutaneous Coronary Intervention

Abstract

Background/Aims: The study was conducted to assess the influence of CYP2C19 polymorphisms on clopidogrel response variability and recurrent cardiovascular (CV) events in Chinese patients undergoing percutaneous coronary intervention (PCI). Methods: Platelet aggregation induced by 5 and 20 µmol/l adenosine diphosphate was measured in 109 patients at baseline, 12 h and 36 h after loading with 300 mg of clopidogrel. The primary end point was recurrent CV events, and the follow-up was scheduled at 1, 3, 6 and 12 months after PCI. The polymorphisms of CYP2C19*2 and CYP2C19*3 were genotyped by DNA sequencing analysis. Results: The maximal aggregation rates and inhibition of platelet aggregation among CYP2C19*1/*1, CYP2C19*1/*2 or *3 and CYP2C19*2/*2 or *3 genotypes were significantly different at 12 and 36 h after clopidogrel loading dose administration. Multiple linear regression analysis demonstrated that CYP2C19*2 and CYP2C19*3 might be predictors of clopidogrel response variability. During the 12-month follow-up, recurrent CV events occurred in 21 (19.63%) patients, and there were 5 (6.47%) deaths, 3 (2.80%) cases of ischemic stroke and 14 (13.1%) cases of acute coronary syndrome. Carriers of at least one CYP2C19 loss-of-function allele (*1/*2 or *3, *2/*2 or *3) incurred a 3.65-fold increase (95% CI 1.07–12.38; p = 0.038) in the risk of recurrent CV events 1 year after PCI compared to noncarriers (*1/*1). Conclusion: Polymorphisms in CYP2C19*2 and CYP2C19*3 contribute to variabilities in clopidogrel responsiveness. Patients carrying at least one CYP2C19 loss-of-function allele (CYP2C19*2, *3) are associated with an increased risk of recurrent CV events undergoing PCI.