%0 Journal Article
%T The CYP2C19*1/*2 Genotype Does Not Adequately Predict Clopidogrel Response in Healthy Malaysian Volunteers
%A Yanti Nasyuhana Sani
%A Lim Sheau Chin
%A Lim Luen Hui
%A Nur Elyana Yazmin Mohd Redhuan Shah Edwin
%A Goh Teck Hwa
%A Victor L. Serebruany
%A Yuen Kah Hay
%J Cardiology Research and Practice
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/128795
%X 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 , CYP2C19*1/*2 and CYP2C19*2/*2 . 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£¿¡Ý£¿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 ¡À 62.1 versus 232.5 ¡À 81.4 versus 147.4 ¡À 87.2 PRU, ) 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. 1. Introduction Adequate platelet inhibition plays a key role in the prevention of recurrent ischemic events in patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Accordingly, the use of clopidogrel as a part of the dual-antiplatelet strategy represents a standard of care in clinical practice [1¨C3]. Recently, the presence of defective alleles of the CYP2C19 enzyme, which is required for the conversion of clopidogrel to its active metabolite, has been associated with lower levels of the active metabolite corresponding in turn to diminished antiplatelet effect and potentially higher rates of adverse cardiovascular events [4, 5]. Consistently, the U. S. Food and Drug Administration (U.S. FDA) has added a black-box warning to the clopidogrel label emphasizing the increased risk of cardiovascular outcomes in patients carrying two loss of function (LoF) CYP2C19 alleles, particularly carriers of
%U http://www.hindawi.com/journals/crp/2013/128795/