Impact of CYP2C19 polymorphism on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing percutaneous coronary intervention.
Impact of CYP2C19 polymorphism on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing percutaneous coronary intervention.
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DOI：
10.5551/jat.18952
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发表时间：
2014-01
影响因子：
4.4
通讯作者：
K. Kaikita;Takamichi Ono;Satomi Iwashita;Naoki Nakayama;Koji Sato;Eiji Horio;Shin-ichi Nakamura;K. Tsujita;S. Tayama;S. Hokimoto;T. Sakamoto;K. Nakao;S. Oshima;S. Sugiyama;H. Ogawa
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文献类型：
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作者：
K. Kaikita;Takamichi Ono;Satomi Iwashita;Naoki Nakayama;Koji Sato;Eiji Horio;Shin-ichi Nakamura;K. Tsujita;S. Tayama;S. Hokimoto;T. Sakamoto;K. Nakao;S. Oshima;S. Sugiyama;H. Ogawa
目的 CYP2C19 功能降低等位基因携带者接受阿司匹林和氯吡格雷双重抗血小板治疗 (DAPT) 后，血小板抑制作用减弱，事件风险增加。本研究的目的是探讨 CYP2C19 基因变异对接受择期经皮冠状动脉介入治疗 (PCI) 患者的血小板功能测试以及凝血和炎症生物标志物的影响。方法 这项前瞻性、观察性、多中心研究连续招募了 104 名接受选择性 PCI 的日本患者。我们在PCI术前、术后即刻以及术后1、2和28天检查了CYP2C19基因型、血小板功能测试、凝血和炎症生物标志物水平以及高敏肌钙蛋白T（hs-TnT）血清水平。结果 104 名入组患者中共有 68 名 (65%) 是 CYP2C19 功能降低等位基因的携带者。使用透光率聚集法和VerifyNow(®) P2Y12系统测量的氯吡格雷血小板聚集(PA)以及携带者在所有时间点的血小板反应性指数(PRI)均显着高于非携带者(p＜0.05)，而凝血和炎症生物标志物或血清hs-TnT的水平没有差异。简单和多重逻辑回归分析确定氯吡格雷 PA 和 PRI 是 CYP2C19 功能降低等位基因携带者的重要预测因子。结论 本研究表明，血小板功能测试（而非凝血、炎症或心脏生物标志物）有助于识别 CYP2C19 功能降低基因变异体的携带者，并监测 DAPT 对接受择期 PCI 的患者的疗效。
AIM Carriers of the reduced-function CYP2C19 allele receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel exhibit diminished platelet inhibition and an increased risk of events. The purpose of this study was to investigate the effects of CYP2C19 gene variants on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing elective percutaneous coronary intervention (PCI). METHODS This prospective, observational, multicenter study enrolled 104 consecutive Japanese patients undergoing elective PCI. We examined the CYP2C19 genotype, platelet function tests, the levels of coagulation and inflammatory biomarkers and the serum levels of high-sensitivity troponin T (hs-TnT) before, immediately after and one, two and 28 days after PCI. RESULTS A total of 68 (65%) of the 104 enrolled patients were carriers of the CYP2C19 reducedfunction allele. On-clopidogrel platelet aggregation (PA), measured using light transmittance aggregometry and the VerifyNow(®) P2Y12 system, and the platelet reactivity index (PRI) were significantly higher at all time points in the carriers than in the noncarriers (p＜0.05), whereas there were no differences in the levels of the coagulation and inflammatory biomarkers or serum hs-TnT. Simple and multiple logistic regression analyses identified on-clopidogrel PA and PRI as being significant predictors of carriers of the CYP2C19 reduced-function allele. CONCLUSIONS The present study suggests that platelet function tests, but not coagulation, inflammatory or cardiac biomarkers, are useful for identifying carriers of CYP2C19 reduced-function gene variants and monitoring the efficacy of DAPT in patients undergoing elective PCI.