Abstract 13656: Functional CYP2C19 Gene Variants are Associated With Both On-clopidogrel Platelet Adhesiveness and Aggregation in Japanese Patients With Coronary Artery Disease
Recent reports have demonstrated effects of CYP2C19 gene variants on the antiplatelet efficacy of clopidogrel and racial differences in frequency of CYP2C19 gene variants, especially between Asian and Caucasian. However, it is unclear whether CYP2C19 gene variants can influence several platelet functions or changes of biomarkers for platelet activation in Japanese patients with coronary artery disease (CAD). In this study, we examined the relation between CYP2C19 gene variants, and platelet functions including platelet adhesiveness, aggregation, and biomarkers for platelet activation in Japanese CAD patients treated with dual antiplatelet therapy with aspirin and clopidogrel (DAPT). We examined CYP2C19 genotype, platelet adhesiveness, residual platelet aggregation (RPA) induced by ADP using light transmittance aggregometry, and platelet biomarkers (von-Willebrand factor (VWF), ADAMTS13, P-selectin, and CD40 ligand) in 181 Japanese CAD patients. Distribution of CYP2C19 phenotype was 35, 49, and 16% in extensive metabolizer (EM; *1/*1), intermediate metabolizer (IM; *1/*2, *1/*3), and poor metabolizer (PM; *2/*2, *2/*3, *3/*3), respectively. On-clopidogrel RPA was higher in PM and IM compared with EM (60.8±9, 55.7±11, and 51.8±42 % in maximum aggregation rate, p<0.05). Platelet adhesiveness was also elevated in PM and IM compared with EM (34±16, 33±18, and 26±19 %, p<0.05). There was a significant positive correlation between RPA and platelet adhesiveness in the total CAD patients (r=0.297, p<0.001, N=161). There were not significant differences among 3 CYP2C19 phenotypes in the levels of plasma VWF (1448±186 in PM, 1571±613 in IM, and 1597±607 mU/mL in EM, p=NS), ADAMTS13 (699±216 in PM, 727±169 in IM, and 738±218 mU/mL in EM, p=NS), P-selectin (291±60 in PM, 365±168 in IM, and 380±275 ng/mL in EM, p=NS), and CD40 ligand (2240±1203 in PM, 2223±1224 in IM, and 2679±1278 pg/mL in EM, p=NS). These findings suggested that CYP2C19 gene variants might influence the platelet function such as platelet adhesiveness and RPA, but not biomarkers for platelet activation in Japanese CAD patients treated with DAPT. These platelet function tests may be useful for predicting CYP2C19 polymorphism and monitoring the efficacy of DAPT in Japanese CAD patients.
- © 2010 by American Heart Association, Inc.