%0 Journal Article
%T Influence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel response
%A Kreutz RP
%A Nystrom P
%A Kreutz Y
%A Miao J
%A Desta Z
%A Breall JA
%A Li L
%A Chiang C
%A Kovacs R
%A Flockhart DA
%A Jin Y
%J Clinical Pharmacology: Advances and Applications
%D 2012
%I Dove Medical Press
%R http://dx.doi.org/10.2147/CPAA.S27822
%X fluence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel response Original Research (3350) Total Article Views Authors: Kreutz RP, Nystrom P, Kreutz Y, Miao J, Desta Z, Breall JA, Li L, Chiang C, Kovacs R, Flockhart DA, Jin Y Published Date February 2012 Volume 2012:4 Pages 13 - 20 DOI: http://dx.doi.org/10.2147/CPAA.S27822 Received: 01 November 2011 Accepted: 05 December 2011 Published: 20 February 2012 Rolf P Kreutz1,2, Perry Nystrom2, Yvonne Kreutz2, Jia Miao2, Zeruesenay Desta2, Jeffrey A Breall1, Lang Li2, ChienWei Chiang2, Richard Kovacs1, David A Flockhart2, Yan Jin2 1Krannert Institute of Cardiology, 2Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA Background: The metabolic activation of clopidogrel is a two-step process. It has been suggested that paraoxonase-1 (PON1) is a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to an active thiol metabolite. Conflicting results have been reported in regard to (1) the association of a common polymorphism of PON1 (Q192R) with reduced rates of coronary stent thrombosis in patients taking clopidogrel and (2) its effects on platelet inhibition in patient populations of European descent. Methods: Blood samples from 151 subjects of mixed racial background with established coronary artery disease and who received clopidogrel were analyzed. Platelet aggregation was determined with light transmittance aggregometry and VerifyNow  P2Y12 assay. Genotyping for cytochrome P450 2C19 (CYP2C19)*2 and *3 and PON1 (Q192R) polymorphisms was performed. Results: Carriers of CYP2C19*2 alleles exhibited lower levels of platelet inhibition and higher on-treatment platelet aggregation than noncarriers. There was no significant difference in platelet aggregation among PON1 Q192R genotypes. Homozygous carriers of the wild-type variant of PON1 (QQ192) had similar on-treatment platelet reactivity to carriers of increased-function variant alleles during maintenance clopidogrel dosing, as well as after administration of a clopidogrel 600 mg loading dose. Conclusion: CYP2C19*2 allele is associated with impaired platelet inhibition by clopidogrel and high on-treatment platelet aggregation. PON1 (Q192R) polymorphism does not appear to be a significant determinant of clopidogrel response.
%K PON1
%K platelet
%K aggregation
%K cytochrome P450 enzymes
%U https://www.dovepress.com/influence-of-paraoxonase-1-q192r-and-cytochrome-p450-2c19-polymorphism-peer-reviewed-article-CPAA