Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Cardiovascular Intervention
Relationship Between CYP2C19 Loss-of-Function Polymorphism and Platelet Reactivities With Clopidogrel Treatment in Japanese Patients Undergoing Coronary Stent Implantation
Tomoyuki NakataMasatoshi MiyaharaKaname NakataniHideo WadaTakashi TanigawaFumihiko KomadaKozo HoshinoToshikazu AokiYuki NishimuraSatoshi TamaruMasaaki ItoMasakatsu Nishikawafor the McLORDD group
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2013 Volume 77 Issue 6 Pages 1436-1444

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Abstract

Background:CYP2C19 loss-of-function genotype (*2 and/or *3 alleles) is related to low responsiveness to clopidogrel, which is a risk factor for ischemic cardiac events. The contribution of these genotypes to platelet reactivity in Japanese patients in a steady state receiving dual antiplatelet therapy after coronary stenting was evaluated. Methods and Results: A total of 155 Japanese patients were classified according to their CYP2C19 loss-of-function genotype. Platelet reactivity was assayed by plasma levels of soluble P-selectin and platelet-derived microparticles, light transmittance aggregometry induced by ADP (ADP-LTA), shear stress-induced platelet aggregometry, vasodilator-stimulated phosphoprotein phosphorylation (VASP) index and the VerifyNow-P2Y12 assay. Linear and logistic regression models were used to assess the associations between CYP2C19 loss-of-function genotype and high on-treatment platelet reactivity. In total, 62 patients (40.0%) were extensive metabolizers (EMs), 70 (45.2%) were intermediate metabolizers (IMs) and 23 (14.8%) were poor metabolizers (PMs). ADP-specific assays (ADP-LTA, the VASP index and VerifyNow-P2Y12) differed according to CYP2C19 genotype, with a significant gene-dose effect (PMs>IMs>EMs). CYP2C19 loss-of-function carrier status was associated with more frequent high platelet reactivity. CYP2C19 loss-of-function genotype alone could explain 12.2%, 14.3%, and 14.7% of the variability in the ADP-LTA, VASP and VerifyNow-P2Y12 assays, respectively. Conclusions:CYP2C19 loss-of-function genotype is associated with more frequent high platelet reactivity, as assessed by ADP-specific platelet function tests, in Japanese patients.  (Circ J 2013; 77: 1436–1444)

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© 2013 THE JAPANESE CIRCULATION SOCIETY
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