CYP2C19基因多态性与ADP诱导的RPA相关关系及两者对CHD患者预后的影响  

Association of CYP2C19 gene polymorphism with RPA by ADP induced and the effect of them on prognosis of patients with CHD

作　　者：王雪 李莹 张清禄 李龙龙 WANG Xue;LI Ying;ZHANG Qing-lu(Department of Laboratory,Weinan Central Hospital,Weinan Shaanxi 714000,China;Department of Laboratory,Xi'an Fourth Hospital,Xi'an Shaanxi 710004,China.)

机构地区：[1]渭南市中心医院检验科,陕西渭南714000 [2]西安市第四医院检验科,陕西西安710004

出　　处：《临床和实验医学杂志》2019年第2期160-164,共5页Journal of Clinical and Experimental Medicine

摘　　要：目的探究CYP2C19基因多态性与ADP诱导的血小板残余活性(RPA)之间的相关关系,以及两者对冠心病(CHD)患者预后的影响。方法回顾性选取于2014年3月至2016年5月就诊渭南市中心医院的204例CHD患者,其中服用氯吡格雷(75 mg/d维持)的稳定性心绞痛(SA)患者100例,服用阿司匹林(100 mg/d)和氯吡格雷(75 mg/d维持)的ACS患者104例。采用全血电阻法检测体内药物浓度稳定后的RPA,加入ADP或花生四烯酸(AA)作为诱导剂。采用CYP2C19基因检测试剂盒-DNA微阵列芯片法检测受试者的CYP2C19基因多态性。平均随访12个月,记录预后情况,根据预后将观察对象分为发生缺血事件组和未发生缺血事件组。根据CYP2C19基因多态性检测结果,分为高代谢组(EM,CYP2C19*1/*1)、中代谢组(IM,CYP2C19*1/*2或*1/*3)和低代谢组(PM,CYP2C19*2/*2,*2/*3或*3/*3)三组。绘制抗血小板治疗药物低反应RPA界值预测CHD患者预后的ROC曲线,对ADP诱导的RPA及CYP2C19基因多态性与的关系采用Kaplan-Meier生存分析。结果 ADP诱导的RPA在EM、IM、PM组间的差异具有显著性(P <0. 05);而AA诱导的RPA在三组间差异无显著差异(P> 0. 05)。发生缺血事件组RPA水平高于未发生缺血事件组,RPA水平与缺血事件发生显著相关(P <0. 05)。ROC分析示ADP诱导的RPA最佳界值为7. 58Ω,对主要缺血事件的特异度是92. 8%,敏感度是69. 6%;以AA诱导的RPA最佳界值为5. 96Ω,对主要缺血事件的特异度99. 4是%,敏感度是82. 6%。生存分析提示,氯吡格雷低反应性对不良事件的发生有显著影响(P <0. 05),而是否为IM或PM及阿司匹林低反应性对缺血性事件发生的影响无统计学意义(P> 0. 05)。结论 CYP2C19基因多态性可影响ADP诱导的RPA的水平,但其对CHD患者缺血事件的发生无显著影响。而ADP诱导的RPA水平与CHD患者缺血事件的发生显著相关。Objective To investigate the relationship between CYP2 C19 gene polymorphism and RPA( residual platelet aggregation rate)induced by ADP,and their effects on the prognosis of CHD( coronary heart disease) patients. Methods 204 patients with CHD treated from March 2014 to May 2016 in our hospital were selected. 100 patients with SA were treated with clopidogrel( 75 mg/d maintenance),104 patients with ACS were treated with aspirin( 100 mg/d) and clopidogrel( 75 mg/d maintenance). The whole blood resistance method was used to detect the RPA in vivo when the concentration of drugs were stable,add ADP or arachidonic acid( AA) as an inducer. The CYP2 C19 gene polymorphism of the subjects was detected by CYP2 C19 gene detection kit-DNAmicro array method. The average follow-up period was 12 months. The prognosis was recorded. According to prognosis,the subjects were divided into ischemic event group and non-ischemic event group. The ROC curve was used to evaluate the prognostic value of CHD patients. Kaplan-Meier survival analysis was used to analyze the relationship between ADP induced polymorphism of CYP2 C19 gene and RPA. Results There was no significant difference between the two groups in age,sex,BMI,number of smokers,platelet count before treatment,basic diseases and drug use( P > 0. 05). The difference of ADP induced RPA between EM( CYP2 C19* 1/* 1),IM( CYP2 C19* 1/* 2 or * 1/* 3) and PM( CYP2 C19* 2/* 2,* 2/* 3 or * 3/* 3) group was statistically significant( P < 0. 05),but there was no significant difference between RPA induced by AA of the two groups( P > 0. 05). The level of RPA in the ischemic event group was higher than that in the non-ischemic event group,and the RPA level was significantly correlated with the ischemic event,and the difference was statistically significant( P < 0. 05). The best predict value of RPA induced by ADP was 7. 58 Ω,specificity was92. 8%,sensitivity was 69. 6%; RPA value induced by AA was 5. 96 Ω,the specificity was 99. 4%,sensitivity was 82. 6%. Survival analysis indicated that th

关 键 词：冠心病 CYP2C19基因多态性 残余血小板活性 

分 类 号：R541.4[医药卫生—心血管疾病] R446.11[医药卫生—内科学]