血浆细胞色素P4502C19基因多态性与皖北汉族急性冠脉综合征患者氯吡格雷抵抗及冠脉介入术后近期预后的关系

The role of cytochrome P4502C19 genetic polymorphism in clopidogrel resistance and prognosis of acute coronary syndrome after percutaneous coronary intervention in Han populations of Northern Anhui

目的:探讨皖北汉族急性冠状动脉综合征(ACS)患者血浆细胞色素P4502C19(CYP2C19)基因多态性分布特征及其与氯吡格雷抵抗(CR)的关系,并评价其对接受经皮冠状动脉介入治疗(PCI)患者近期预后的影响。方法:入选298例住院并接受阿司匹林和氯吡格雷双联抗血小板治疗的皖北汉族ACS患者。采用基因芯片技术和荧光定量PCR检测每位患者CYP2C19基因的多态性,根据结果分为快代谢型(CYP2C19*1/*1)、中等代谢型(CYP2C19*1/*2,CYP2C19*1/*3)和慢代谢型(CYP2C19*2/*2,CYP2C19*2/*3,CYP2C19*3/*3)3组。采用光学比浊法检测每位患者服用氯吡格雷前和用药后7d的血小板聚集率(PAR),以用药前后差值≤10%定义为CR。所有患者均行PCI,计算血管病变支数和Gensini评分。对患者住院期间严密观察,出院后通过电话或门诊随访≥3个月。结果:慢代谢型组较中等代谢型组,中等代谢型组较快代谢型组发生CR的比例均增高(均P<0.05)。3组冠状动脉病变支数和Gensini评分差异均无统计学意义。多因素Logistic回归分析显示,携带CYP2C19突变基因是ACS患者发生CR的独立预测因子(OR:2.122,P<0.01)。随访3个月以上,慢代谢型组和中等代谢型组较快代谢型组有更高的心血管事件发生率(P<0.05)。结论:皖北汉族ACS患者血浆CYP2C19基因多态性与CR的发生存在相关性,且基因突变增加了患者PCI术后心血管事件发生的风险,影响临床预后。

Objective：To explore the characteristics of cytochrome P4502C19（CYP2C19）distribution and the relationship between genetic polymorphism and clopidogrel resistance（CR）,as well as short-term prognosis of acute coronary syndrome（ACS）after percutaneous coronary intervention（PCI）occurring to Han patients in the Northern Anhui province.Method：A total of 298 patients with ACS receiving aspirin and clopidogrel dual antiplatelet therapy were enrolled in this study.We used gene chip technology and fluorescence quantitative PCR to detect CYP2C19 gene polymorphism.The patients were divided into three groups：fast metabolism group with CYP2C19＊1/＊1,secondary metabolism group with CYP2C19＊1/＊2and CYP2C19＊1/＊3,and slow metabolic group with CYP2C19＊2/＊2,CYP2C19＊2/＊3and CYP2C19＊3/＊3.Optical turbidimetric method was applied to detect platelet aggregation rate（PAR）seven days before and after receiving clopidogrel therapy.Patients with less than 10% difference after the treatment was defined to have CR.Then PCI were performed on all patients,and vascular lesions counts as well as Gensini score were calculated.Patients were closely observed in hospital and further tracked after discharge by phone or outpatient follow-up not less than 3months.Result：The number of patients with CR in the slow metabolism was higher than that in the secondary metabolic group,while the number in the secondary metabolic group was higher than that in the fast metabolic group.However,no statistically significant difference was found in the coronary artery lesions and Gensini score among the three groups.Multi-factor logistic regression analysis indicated that carrying mutation CYP2C19 gene was an independent predictor of ACS in patients with CR（OR：2.122,P〈0.01）.The follow-up study of the discharged patients in all three groups after three months indicated that the slow metabolism group and the secondary metabolism group had a higher chance of cardiovascular events compared with the fast metabolism group.Conclusion：Correlation is found between CYP2C19 genetic polymorphism and CR.Genetic mutation increases the risk of postoperative cardiovascular events in patients after PCI treatment,and effects the clinical prognosis.