Tabata Noriaki, Hokimoto Seiji, Akasaka Tomonori, Arima Yuichiro, Kaikita Koichi, Kumagae Naoki, Morita Kazunori, Miyazaki Hiroko, Oniki Kentaro, Nakagawa Kazuko, Matsui Kunihiko, Ogawa Hisao
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan.
Thromb Res. 2014 Nov;134(5):939-44. doi: 10.1016/j.thromres.2014.07.039. Epub 2014 Aug 14.
There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients with dual antiplatelet therapy. Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event, but the association between the possession of CYP2C19 loss-of-function (LOF) alleles and clinical outcome according to the presence of CKD is poorly understood. The aim of this study was to investigate whether CKD status modifies the association of CYP2C19 polymorphism in predicting outcomes in a prospective cohort study.
We enrolled 331 patients following coronary stent implantation. Patients were divided into two groups: CKD (n=154) and non-CKD (n=177). Platelet reactivity and CYP2C19 polymorphism were examined. The subjects were further divided into two groups according to the possession of CYP2C19 LOF alleles: carriers and non-carriers. Patients were followed up and clinical events were evaluated according to CKD and carrier status.
The proportion of high platelet reactivity was significantly higher in carriers than in non-carriers in both CKD (42.4% versus 21.7%; P=0.016) and non-CKD groups (34.3% versus 3.7%; P<0.001). In the non-CKD group alone, the incidence of cardiovascular events was significantly higher in carriers than in non-carriers (13.7% versus 1.7%; P=0.013). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers than in non-carriers in the non-CKD group (log-rank test: P=0.013) and there was no significant difference in the CKD group (log-rank test: P=0.591). Multivariate analysis identified carriers as an independent predictor of cardiovascular events only in the non-CKD group alone (hazard ratio: 8.048; 95% confidence interval: 1.066 to 60.757; P=0.043).
CYP2C19 polymorphism significantly correlates with clinical outcome in non-CKD patients, and CKD status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation.
关于CYP2C19基因多态性对双重抗血小板治疗患者临床结局的影响存在一些争议。慢性肾脏病（CKD）与心血管事件风险增加相关，但根据CKD的存在情况，携带CYP2C19功能丧失（LOF）等位基因与临床结局之间的关联尚不清楚。本研究的目的是在一项前瞻性队列研究中调查CKD状态是否会改变CYP2C19基因多态性在预测结局方面的关联。
我们纳入了331例冠状动脉支架植入术后的患者。患者分为两组：CKD组（n = 154）和非CKD组（n = 177）。检测血小板反应性和CYP2C19基因多态性。根据是否携带CYP2C19 LOF等位基因，将受试者进一步分为两组：携带者和非携带者。对患者进行随访，并根据CKD和携带者状态评估临床事件。
在CKD组（42.4%对21.7%；P = 0.016）和非CKD组（34.3%对3.7%；P < 0.001）中，携带者的高血小板反应性比例均显著高于非携带者。仅在非CKD组中，携带者的心血管事件发生率显著高于非携带者（13.7%对1.7%；P = 0.013）。Kaplan-Meier分析显示，非CKD组中携带者发生心血管事件的概率显著高于非携带者（对数秩检验：P = 0.013），而CKD组无显著差异（对数秩检验：P = 0.591）。多因素分析仅在非CKD组中确定携带者是心血管事件的独立预测因素（风险比：8.048；95%置信区间：1.066至60.757；P = 0.043）。
CYP2C19基因多态性与非CKD患者的临床结局显著相关，且CKD状态会改变CYP2C19基因多态性在预测冠状动脉支架植入术后临床结局方面的关联。
