Association between CYP2C19 G681A gene polymorphisms and clopidogrel resistance in the Han population of North China with coronary atherosclerotic heart disease

Objective To elucidate the preliminary association between Cytochrom P450 2C19( CYP2C19) gene G681 A polymorphisms and CR in the Han population of North China with coronary artery disease( CAD).Methods A total of 136 patients( 73 with acute coronary sydrome and 60 with stable angian pectoris) were enrolled.The vasodilator-stimulated phosphoprotein( VASP) phosphorylation state was determined in all patients received a 600 mg loading dose of Clopidogrel.Patients enrolled were divided into CR group and Non-CR group according to the value of VASP index.VASP index of≥50% was regarded as CR.The presence of CYP2C19G681A polymorphisms was determined by polymerase chain reaction-restriction fragment length polymorphism( PCR-RFLP) analysis combined with sanger dideoxy mediated chain termination method.Then the distribution of the frequencies of genotypes and alleles among CR and NCR groups was analyzed.Results There were 80 patients in the CR group, indicating the occurrence of CR at a rate of 58.82%.Compared with SAP,patients with ACS were at a higher rate of occurrence of CR( 67.1% vs.49.2%,P 0.05).The genotype( GG / GA / AA) distribution of the CYP2C19 G681A gene polymorphisms were 47.54%,46.22%,6.24% and 69.63%,26.80%,3.57% in the CR and NCR groups, respectively.Statistically significant difference was observed between CR and NCR groups for distribution of the genotypes( P 0.05).Frequency of A allele was significantly higher in CR group than in NCR group( 29.37% vs.16.96%,P 0.05),A allele carriers were more likely to develop CR( OR = 2.04,95% CI: 1.12-3.71,P 0.05).Logistic regression analysis adjusted for the presence of traditional risk factors including age,gender,BMI, hypertention,type2 diabetes,the CYP2C19G681A polymorphism resulted an independent risk factor for CR( OR = 3.259,95% CI: 1.476-6.764,P 0.001).Conclusion CYP2C19 gene G681A single nucleotide polymorphism is associated with the occurrence of CR; A allele might be an important genetic risk factor for the development of CR.