CYP2C19基因多态性对大连地区汉族人急性冠状动脉综合征患者经皮冠状动脉介入治疗术后远期预后影响

Effect of CYP2C19 gene polymorphism on the prognosis in acute coronary syndrome after percutaneous coronary intervention in Han population from Dalian

目的探讨氯吡格雷药物代谢相关CYP2C19基因多态性对急性冠状动脉综合征(ACS)患者行经皮冠状动脉介入治疗(PCI)术后远期预后的影响。方法选取大连市中心医院2012年1月至2014年1月诊断为ACS的大连地区汉族人,经PCI治疗并在围手术期行CYP2C19多态性(*1、*2和*3)基因型检测的患者共809例,其中急性ST段抬高型心肌梗死178例,急性非ST段抬高心肌梗死105例,不稳定型心绞痛526例。依CYP2C19基因型将患者分为快代谢(EM)组(基因型*1/*1)、中间代谢(IM)组(基因型*1/*2、*1/*3)和慢代谢(PM)组(基因型*2/*2、*3/*3、*2/*3)。所有患者术后随访观察至少24个月,记录随访期间发生的主要心血管不良事件(MACE),最后对三组患者临床资料和MACE进行比较分析。结果790例患者完成随访观察,19例失访,CYP2C19的基因型为(*1/*1)350例(43.2%)、(*1/*2)318例(39.3%)、(*1/*3)42例(5.2%)、(*2/*2)77例(9.5%)、(*2/*3)21例(2.6%)、(*3/*3)1例(0.1%)。EM组350例(43.2%),IM组360例(44.5%),PM组99例(12.2%)。三组患者的年龄、性别、高血压、糖尿病、吸烟史等基本临床资料比较差异无统计学意义(P>0.05),介入干预的冠状动脉状况及诊断构成差异无统计学意义(P>0.05)。三组共发生MACE26例(3.3%),其中靶血管再次血运重建8例,EM组、IM组和PM组分别为3、3和2例;非致死性心肌梗死2例,EM组、IM组、PM组分别为0、1和1例;死亡15例,EM组、IM组、PM组分别为6、7和2例;亚急性支架内血栓1例,发生在IM组。PM组总不良心血管事件发生率稍高于EM组和IM组,但差异无统计学意义(P>0.05)。三组患者支架内血栓、靶血管再次血运重建、非致死性心肌梗死、死亡差异均无统计学意义(P>0.05)。结论CYP2C19基因多态性与大连地区汉族人急性冠状动脉综合征患者PCI术后长期预后无明显相关。

Objective To observe the relationship between CYP2C19 gene polymorphisms and major adverse cardiovascular events in the patients of acute coronary syndrome (ACS) who accepted percutaneous coronary intervention (PCI) in Han population from Dalian. Methods A total 809 cases with ACS who had undergone PCI in the cardiology department of Dalian Municipal Central Hospital from Janurary 2012 to Janurary 2014 were selected. Among 809 cases of ACS, there were 178 cases of acute ST segment elevation myocardial infarction (STEMI), 105 cases of acute non ST segment elevation myocardial infarction (NSTEMI) and 526 cases of unstable angina. The patients were divided into three groups according to their CYP2C19 genotype.CYP2C19 genotype (*1/*1) were classified as extensive metabolizers (EM group), CYP2C19 genotype (*1/*2、*1/* 3) were classified as intermediate metabolizers(IM group) and CYP2C19 genotype (*2/*2、*3/*3、*2/*3) were classified as poor metabolizers (PM group). The occurrence of major adverse cardiovascular events at least 24 months was observed. Results Seven hundred and ninety patients finished the follow-up at least 24 months, 19 patients lost in follow-up, 350 cases (43.2%) were CYP2C19 (*1/*1), 318 cases (39.3%) were CYP2C19(*1/*2), 42 cases(5.2%) were CYP2C19 (*1/*3), 77 cases (9.5%) were CYP2C19 (*2/*2), 21 case(2.2%)were CYP2C19 (*2/*3), and 1 case (0.1%) was CYP2C19(*3/*3), 350 cases (43.2%) were classified as EM group, 360 cases (44.5%) were classified as IM group, and 99 cases(12.2%)were classified as PM group. No significant difference in age, gender, hypertention, diabetes mellitus, smoking was shown among three groups (P > 0.05). The rate of MACE were 3.3%, 8 cases had target lesion revascularization(EM group 3 cases, IM group 3 cases, PM group 2 cases), 2 cases had non-fatal myocardial infarction (IM group 1 case, PM group 1 case), 15 cases were died(EM group 6 cases, IM group 7 cases, PM group 2 cases), 1 case had subacute stent thrombosis in IM group. The rates of MACE were higher in PM group (5.1%) than those in EM group(2.65%) and IM group (3.41%), but there was no significant difference in three groups (P > 0.05). There was no significant difference in the rate of target lesion revascularization, thrombus in stent, non-fatal myocardial infarction and death among three groups(P > 0.05). Conclusions There is no significant correlation between CYP2C19 gene polymorphism and long-term prognosis in patients with ACS who accepte PCI treatment in Han population from Dalian.