The CYP2C19*1/*2 Genotype Does Not Adequately Predict Clopidogrel Response in Healthy Malaysian Volunteers

Abstract

Background. TheCYP2C19*2allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whetherCYP2C19*2alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers.Methods. Ninety volunteers were genotyped forCYP2C19*2andCYP2C19*3alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely,CYP2C19*1/*1(n=17),CYP2C19*1/*2(n=21),andCYP2C19*2/*2(n=7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230.Results. Following clopidogrel intake,CYP2C19*2/*2carriers had a significantly higher mean PRU compared to theCYP2C19*1/*2andCYP2C19*1/*1(291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU,P<0.001) carriers. Almost half of the participants (46.7%) were found to be nonresponders (3 wereCYP2C19*1/*1, 11 wereCYP2C19*1/*2, and 7 wereCYP2C19*2/*2).Conclusion. In healthy Malaysian volunteers,CYP2C19*2allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers ofCYP2C19*2/*2, but also in the carriers ofCYP2C19*1/*2andCYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy.