title: The CYP2C19(∗)1/(∗)2 Genotype Does Not Adequately Predict Clopidogrel Response in Healthy Malaysian Volunteers.
abstract: Background. The CYP2C19∗2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19∗2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19∗2 and CYP2C19∗3 alleles. 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), and CYP2C19∗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/∗2 carriers had a significantly higher mean PRU compared to the CYP2C19∗1/∗2 and CYP2C19∗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 were CYP2C19∗1/∗1, 11 were CYP2C19∗1/∗2, and 7 were CYP2C19∗2/∗2). Conclusion. In healthy Malaysian volunteers, CYP2C19∗2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19∗2/∗2, but also in the carriers of CYP2C19∗1/∗2 and CYP2C19∗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.
authors: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia ; Sarawak General Hospital, Clinical Research Centre, 93586 Kuching, Sarawak, Malaysia.
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