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CYP2C19 基因型并不影响冠心病患者的长期预后。

The CYP2C19 genotype does not impact the long-term prognosis of patients with coronary artery disease.

机构信息

Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China.

出版信息

Atherosclerosis. 2013 Mar;227(1):106-11. doi: 10.1016/j.atherosclerosis.2012.12.028. Epub 2013 Jan 2.

Abstract

BACKGROUND

Cytochrome P450 (CYP) 2C19 plays a key role in clopidogrel activation and thus impacts the clinical outcome of patients with coronary artery disease (CAD). However, the majority of patients with CAD gradually discontinue clopidogrel after one year of discharge. This study explored whether the CYP2C19 gene polymorphism was associated with clinical events in patients with CAD after one year of discharge.

METHOD

Between July 2008 and July 2009, 506 patients with CAD that was confirmed by coronary angiography were enrolled in this study, and their CYP2C19 genotype was determined. The primary endpoint events included cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. The secondary endpoint events included the components of the primary endpoint events, all-cause mortality and recurrent revascularisation.

RESULT

The baseline clinical characteristics of CYP2C19*2-mutation carriers (homozygous *2/*2, n = 49; heterozygous *1/*2, n = 222) and non-carriers (wild-type allele *1/1, n = 235) were comparable. The follow-up results showed that the incidence of adverse cardiovascular events within one year of discharge was significantly higher in carriers of the CYP2C192 homozygous genotype (*2/2) than non-carriers (12.24% vs. 3.83%, adjusted hazard ratio (HR) 4.651, 95% confidence interval (CI) 1.566-13.814, p = 0.006). However, the follow-up results after one year of discharge showed that the risk of the CYP2C192 homozygous genotype were significantly reduced. New primary endpoint events during the second year after discharge had no significant correlation with the CYP2C19 genotype.

CONCLUSION

The risk of cardiovascular events in CAD patients with a homozygous CYP2C192 mutation was significantly higher than in other patients within the first year after discharge. However, the adverse impact of the CYP2C192 polymorphism was significantly reduced after one year of discharge.

摘要

背景

细胞色素 P450(CYP)2C19 在氯吡格雷的激活中起着关键作用,因此影响了冠心病(CAD)患者的临床结局。然而,大多数 CAD 患者在出院后一年内逐渐停用氯吡格雷。本研究旨在探讨 CYP2C19 基因多态性与出院后一年 CAD 患者临床事件的关系。

方法

本研究纳入了 2008 年 7 月至 2009 年 7 月期间经冠状动脉造影证实的 506 例 CAD 患者,并检测了其 CYP2C19 基因型。主要终点事件包括心血管死亡、非致死性心肌梗死和非致死性卒中等。次要终点事件包括主要终点事件的组成部分、全因死亡率和再次血运重建。

结果

CYP2C192 突变携带者(纯合突变2/2,n=49;杂合突变1/2,n=222)和非携带者(野生型等位基因1/1,n=235)的基线临床特征相当。随访结果显示,出院后一年内,CYP2C192 纯合基因型(*2/2)携带者的不良心血管事件发生率明显高于非携带者(12.24% vs. 3.83%,调整后 HR 4.651,95%CI 1.566-13.814,p=0.006)。然而,出院后一年的随访结果显示,CYP2C192 纯合基因型携带者的风险显著降低。出院后第二年的新主要终点事件与 CYP2C19 基因型无显著相关性。

结论

在出院后一年内,CYP2C192 纯合突变的 CAD 患者发生心血管事件的风险明显高于其他患者。然而,CYP2C192 多态性的不良影响在出院一年后显著降低。

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