Research Article

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

Published: February 13, 2015
Genet. Mol. Res. 14 (1) : 1434-1442 DOI: 10.4238/2015.February.13.22

Abstract

We investigated the correlation between genetic polymorphisms of cytochrome P450 enzyme genes and the outcome of clopidogrel treatment in 118 coronary disease patients after percutaneous coronary intervention at the Chinese PLA General Hospital. Patients were divided into an ischemia event relapse group (IERG) and a non-IERG group (NIERG) based on relapse of ischemia events within 6 months after percutaneous coronary intervention. Ischemia occurred in 26.27% of patients. Thromboelastogram platelet mapping results showed that compared with the NIERG, the ADP-induced platelet inhibition ratio in the IERG was significantly lower (31.33 ± 24.91% vs 54.68 ± 26.63%, P CYP3A5*3 (41.98 ± 29.33% vs 52.89 ± 26.49%), CYP2C19*2 (43.15 ± 27.97% vs 55.89 ± 26.71%), and P2Y12*1 (38.74 ± 24.36% vs 52.19 ± 28.58%) was lower than patients with the wild-type alleles. The frequency of ischemia event relapse in patients with the mutant alleles CYP3A5*3 and CYP2C19*2 was significantly higher than patients carrying the G/G genotype; however, there was no significant difference between patients carrying the T/T genotype and C allele of P2Y12*1. Thus, coexisting polymorphisms of CYP3A5*3 and 2C19*2, but not P2Y12*1, play an important role in the variability of clopidogrel’s curative effect.

We investigated the correlation between genetic polymorphisms of cytochrome P450 enzyme genes and the outcome of clopidogrel treatment in 118 coronary disease patients after percutaneous coronary intervention at the Chinese PLA General Hospital. Patients were divided into an ischemia event relapse group (IERG) and a non-IERG group (NIERG) based on relapse of ischemia events within 6 months after percutaneous coronary intervention. Ischemia occurred in 26.27% of patients. Thromboelastogram platelet mapping results showed that compared with the NIERG, the ADP-induced platelet inhibition ratio in the IERG was significantly lower (31.33 ± 24.91% vs 54.68 ± 26.63%, P CYP3A5*3 (41.98 ± 29.33% vs 52.89 ± 26.49%), CYP2C19*2 (43.15 ± 27.97% vs 55.89 ± 26.71%), and P2Y12*1 (38.74 ± 24.36% vs 52.19 ± 28.58%) was lower than patients with the wild-type alleles. The frequency of ischemia event relapse in patients with the mutant alleles CYP3A5*3 and CYP2C19*2 was significantly higher than patients carrying the G/G genotype; however, there was no significant difference between patients carrying the T/T genotype and C allele of P2Y12*1. Thus, coexisting polymorphisms of CYP3A5*3 and 2C19*2, but not P2Y12*1, play an important role in the variability of clopidogrel’s curative effect.