CYP2C19 681G>A和636G>A基因多态性对冠心病行PCI术后服用氯吡格雷患者血小板活性及临床预后的影响

Effect of CYP2C19 681G>A and 636G>A Polymorphisms on Residual Platelet Reactivity and Adverse Clinical Events in Clopidogrel-Treated Survivors after Percutaneous Coronary Intervention

目的观察CYP2C19 681G>A、636G>A(CYP2C19*2、*3)基因多态性对冠心病行冠状动脉介入术后服用氯吡格雷患者残余血小板活性及临床预后的影响。方法入选2011年6月至2011年12月因冠心病行经皮冠状动脉介入术者共202例,根据CYP2C19基因型不同,分为正常纯合子组78例(CYP2C19*1/*1)、单突变基因携带组100例(CYP2C19*1/*2、CYP2C19*1/*3)、双突变基因携带组24例(CYP2C19*2/*2、CYP2C19*2/*3),对比三组间临床基本资料、残余血小板活性、半年内主要心血管事件及出血事件发生率。结果三组间仅钙离子拮抗剂使用率存在差异(正常纯合子组、单突变基因携带组和双突变基因携带组分别为15.4%、29.0%和45.8%,P=0.007),其余临床资料基本相似。口服氯吡格雷5天(正常纯合子组、单突变基因携带组和双突变基因携带组分别为51.60%±17.21%、55.89%±14.92%和62.00%±9.75%,P=0.060)及3个月时(49.45%±16.90%、55.98%±19.03%和57.64%±18.42%,P=0.248)二磷酸腺苷诱导的血小板聚集率在三组间均未见明显差异。双突变基因携带组半年内非致死性心肌梗死发生率明显升高(正常纯合子组、单突变基因携带组和双突变基因携带组分别为0%、0%和8.3%,P=0.001),而心绞痛复发、支架内血栓形成、急性左心衰竭、心源性死亡及出血事件发生率三组间未见明显差异。结论 CYP2C19 681G>A和CYP2C19 636G>A基因多态性与经皮冠状动脉介入术后服用氯吡格雷的冠心病患者早期残余血小板活性及临床预后相关。

Aim To observe the effect of CYP2C19 681G〉A and 636G〉A （CYP2C19＊2 and ＊3） polymorphisms on residual platelet reactivity and adverse clinical events in clopidogrel-treated survivors after percutaneous coronary intervention （PCI）. Methods 202 patients with coronary heart disease who received PCI and treated with clopidogrel were enrolled in our study from Jun 2011 to Dec 2011. Based on the number of the CYP2C19 mutation allele, patients were divided into normal group（n78, CYP2C19 ＊1/＊1）, one mutation allele group（n100, CYP2C19 ＊1/＊2、CYP2C19 ＊1/＊3） and two mutation alleles group（n24, CYP2C19 ＊2/＊2、CYP2C19 ＊2/＊3）. Baseline data, residual platelet reactivity, major adverse cardiac events and bleeding within half a year were observed. Results There was no significant difference on baseline data among the groups besides Calcium channel blocker （normal group, one mutation allele group, two mutation alleles group： 15.4%, 29.0% and 45.8%, P0.007）. Adenosine diphosphate induced platelet aggregations had no difference among all groups,no matter within 5 days（normal group, one mutation allele group, two mutation alleles group： 51.60%±17.21%, 55.89%±14.92% and 62.00%±9.75%, P0.060） or 3 months（normal group, one mutation allele group, two mutation alleles group： 49.45%±16.90%, 55.98%±19.03%, 57.64%±18.42%, P0.248）. The incidence of nonfatal myocardial infarction was higher in two mutation alleles group than the other groups（normal group, one mutation allele group, two mutation alleles group： 0%, 0% and 8.3%, P0.001） whereas, the incidence of angina recurrence, stent thrombosis, acute heart failure, cardiac death and the bleeding had no difference among all groups. Conclusion Among the patients who received PCI and treated with clopidogrel, CYP2C19 681G〉A and 636G〉A polymorphisms appear to affect prophase residual platelet reactivity and cardiovascular events.