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首页> 外文期刊>Circulation journal >Relationship Between CYP2C19 Loss-of-Function Polymorphism and Platelet Reactivities With Clopidogrel Treatment in Japanese Patients Undergoing Coronary Stent Implantation
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Relationship Between CYP2C19 Loss-of-Function Polymorphism and Platelet Reactivities With Clopidogrel Treatment in Japanese Patients Undergoing Coronary Stent Implantation

机译：CYP2C19功能丧失的多态性与氯吡格雷治疗日本冠状动脉支架植入患者的血小板反应性之间的关系

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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)
机译：背景： ？ CYP2C19功能丧失的基因型（* 2和/或* 3等位基因）与对氯吡格雷的反应性低有关，氯吡格雷是缺血性心脏病的危险因素。在冠状动脉支架置入术中接受双重抗血小板治疗的稳定状态的日本患者中，评估了这些基因型对血小板反应性的贡献。方法和结果：共有155名日本患者根据其CYP2C19功能丧失基因型进行了分类。血小板反应性通过血浆中可溶性P-选择蛋白和血小板衍生的微粒水平，ADP诱导的透光度凝集测定（ADP-LTA），剪切应力诱导的血小板凝集测定，血管舒张剂刺激的磷蛋白磷酸化（VASP）指数和VerifyNow- P2Y12测定。使用线性和逻辑回归模型评估CYP2C19功能丧失基因型与治疗中高血小板反应性之间的关联。共有62例患者（40.0％）为广泛代谢者（EMs），70例（45.2％）为中度代谢者（IMs），23例（14.8％）为弱代谢者（PMs）。根据CYP2C19基因型，ADP特异性测定（ADP-LTA，VASP指数和VerifyNow-P2Y12）有所不同，具有显着的基因剂量效应（PMs> IMs> EMs）。 CYP2C19功能丧失者的携带者状态与更频繁的高血小板反应性相关。单独的CYP2C19功能丧失基因型可以分别解释ADP-LTA，VASP和VerifyNow-P2Y12检测的变异性的12.2％，14.3％和14.7％。结论： CYP2C19功能丧失的基因型与日本人患者通过ADP特异性血小板功能测试评估的更频繁的高血小板反应性相关（Circ J？2013; 77：1436-1444）。

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