Study on the effect of CYP2C19 genetic polymorphism and plasma concentration on clopidogrel resistance

At present, the mechanism for clopidogrel resistance (CR) is incompletely understood. Here, we aimed to analyze of the association of plasma concentration of clopidogrel active metabolites (CAM) and CYP2C19 genetic polymorphism with CR. We assigned 77 patients to receive CLP at a loading dose of 300mg on day 1, followed by 75mg per day from day 2 to day 6. Three peripheral venous blood samples were collected for analysis. Our results showed that plasma concentration of CAM in extensive metabolizers (EMs) group (2.48(1.31, 5.67) ng/mL) was higher than that in intermediate metabolizers (IMs) group (1.44(1.18,3.55) ng/mL) and that in poor metabolizers (PMs) (1.18(1.12,1.33) ng/mL) group was the lowest (H=14.58, P=0.001). Besides, the incidence of CR in EMs group(11.1%) was lower than that in IMs group (20.0%) and that in IMs group was lower than that in PMs group (45.5%) (chi(2)=6.344, P=0.042). In addition, our findings confirmed that the incidence of chest tightness in IMs group (40.0%) and PMs group (50.0%) was higher than that in EMs group (9.1%) (P=0.015). Over the follow-up period, it was found that CYP2C19 and plasma concentration of CAM were related to the incidence of chest tightness. Our findings indicated that in addition to CYP2C19, plasma concentration of CAM may be an important factor in predicting CR.