CYP2C19*2 and other genetic variants affecting platelet response to clopidogrel in patients undergoing percutaneous coronary intervention.

INTRODUCTION

Information regarding any possible additional effect of genetic variants other than CYP2C19*2 on platelet reactivity in patients undergoing percutaneous coronary intervention (PCI), while on dual antiplatelet therapy, is sparse.

MATERIALS AND METHODS

Genotyping for CYP2C192, CYP2C1917, CYP2C93, CYP2B65, ABCB1 and P2RY12 (c.-217+2739T>C) variants was performed in 146 consecutive PCI patients receiving clopidogrel. Platelet reactivity was assessed by the Verify Now P2Y12 point-of-care assay and high on-treatment platelet reactivity (HTPR) was defined as a Platelet Reactivity Unit (PRU)≥235.

RESULTS

We identified 65(44.5%) patients with HTPR and 38(26%) carriers of at least one CYP2C192 allele, which had higher platelet reactivity compared to non-carriers [least square (LS) mean difference 44.5, 95%CI 15.8-77.3, p=0.003]. In the entire study population, the presence of at least one CYP2C192 or P2RY12 allelic variant was independently associated with HTPR (OR=3.02, 95%CI 1.16-7.86, p=0.023 and OR=3.11, 95%CI 1.03-9.39, p=0.05 respectively). In CYP2C192 non-carriers, carriers of at least one CYP2B65 allelic variant had higher platelet reactivity compared to the remainders (LS mean difference 35.6, 95%CI 3.7-67.6, p=0.03) and the presence of at least one CYP2B6*5 or P2RY12 allelic variant was independently associated with HTPR (OR=3.26, 95%CI 1.08-9.86, p=0.04 and OR=4.27, 95%CI 1.11-16.4, p=0.04 respectively).

CONCLUSIONS

Apart from the CYP2C192, other genetic variants involved in clopidogrel metabolism and action like CYP2B65 and P2RY12 seem to have an important association with HTPR.