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Influence of CYP2C19*2 and *3 loss-of-function alleles on pharmacodynamic effects of standard- and high-dose clopidogrel in East Asians undergoing percutaneous coronary intervention: the results of the ACCEL-DOUBLE-2N3 study.


J Thromb Haemost. 2013 Mar 21;


Authors: Jeong YH, Abadilla KA, Tantry US, Park Y, Koh JS, Kwak CH, Hwang JY, Gurbel PA


Abstract

Carriage of the cytochrome P450 (CYP) 2C19 loss-of-function (LoF) polymorphism has been associated with high on-treatment platelet reactivity (HPR) and an increased risk of ischemic event occurrence in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI) [1]. Although there are multiple CYP2C19 alleles associated with null function (i.e. *2-*8), the treatment strategy to overcome LoF allele effect was mostly based on the CYP2C19*2 LoF allele [2]. There is a marked interethnic difference in the frequency of poor metabolizers between East Asians (13-30%) and Caucasians (<5%). The CYP2C19*2 (rs4244285, c.681G>A in exon 5, splice site mutation) and *3 (rs4986893, c.636G>A in exon 4, a premature stop codon) alleles account for LoF polymorphism in East Asians, whereas most of LoF polymorphism in Caucasians consist of the CYP2C19*2 allele with extremely rare *3 carriage. The effect of the CYP2C19*3 allele on the enzyme activity appeared greater than the CYP2C19*2 allele in several studies [3,4]. © 2013 International Society on Thrombosis and Haemostasis.

PMID: 23517020 [PubMed - as supplied by publisher]