The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes

Background The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Methods Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value Results Regarding clopidogrel response, 62 patients (76.5%) were clopidogrel responders and 19 were non-responders (23.5%). Mean PRU value and the percentage of platelet inhibition were 170.0±50.9 PRU and 28.6±19.9%, respectively. The effects of the CYP2C19*2 polymorphisms on PRU (166.0±50.8 vs. 190.7±48.2, pCYP2C19*1/*1 than those in CYP2C19*1/*2+CYP2C19*2/*2 (16.2% vs. 53.8% p0.05). Based on the logistic regression analysis, CYP2C19*2 (OR: 4.365, CI: 1.25–17.67, p=0.022) was an independent predictor of HPR at Conclusions The reactivity of the on-clopidogrel platelet in the early phase of ACS is influenced primarily by the CYP2C19 polymorphisms. We believe that the findings of the present study could supply additional evidence regarding the clinical appropriateness of the CYP2C19 genetic testing for designing suitable antiplatelet therapy in the early phase of ACS.