残余血小板活性和CYP2C19多态性与急性冠状动脉综合征患者临床预后的关系  

The impact of residual platelet activity and CYP2C19 polymorphism on the prognosis of acute coronary syndrome patients

作　　者：乔蕊[1] 杨硕[1] 李蕾[2] 张捷[1] 

机构地区：[1]北京大学第三医院检验科,100191 [2]北京大学第三医院心内科,100191

出　　处：《中华检验医学杂志》2016年第12期911-916,共6页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金（81550041）

摘　　要：目的：评价RPA和CYP2 C19基因多态性与ACS临床缺血事件发生的相关性和对临床预后的影响。方法病例对照研究。入选接受氯吡格雷和阿司匹林治疗的ACS患者202例[男66％，（63±11）岁]，使用全血电阻法方法检测RPA，并测定每个患者CYP2C19多态性。平均随访16个月记录临床缺血事件的发生。采用ROC曲线定义RPA判断抗血小板药物低反应的截断值；RPA和CYP2C19多态性与临床结局的关系评价采用 Kaplan－Meier 生存分析。结果入选患者中CYP2C19＊2型基因（681G＞A）的携带率为52．5％，＊3型基因（636G＞A）的携带率为12．9％。二磷酸腺苷（ ADP）诱导的RPA在CYP2C19＊2或＊3型的纯合子组、杂合子组和野生型组间存在显著性差异（χ^2＝9．318，P＝0．009）；而花生四烯酸（ AA）诱导的RPA（χ^2＝2．441，P＝0．295）和缺血事件的发生率（χ^2＝0．513，P＝0．774）在三组间无显著性差异。随访中18例（9％）患者发生了缺血事件，缺血事件组ADP和AA诱导的RPA高于与未发生缺血事件组[（8．6±4．8）Ω比（5．2±3．7）Ω， P＝0．013；（8．6±6．8）Ω比（1．6±3．7）Ω，P＜0．001）]。 ROC分析显示以6．5Ω（ ADP为诱导剂）和2．5Ω（ AA为诱导剂）为RPA截断值，对缺血事件发生的阴性预测值分别为97％和96％，阳性预测值分别为16％和29％。生存分析显示是否为氯吡格雷低反应，缺血事件发生的危险存在显著性差异（HR＝2．86，χ^2＝11．27，P＝0．0008）；而是否为阿司匹林低反应（HR ＝1．77，χ^2＝1．74，P＝0．19）和是否携带CYP2C19＊2或＊3型基因（HR＝0．89，χ^2＝0．12，P＝0．73），缺血事件发生的危险存不存在显著性差异。结论 ACS患者氯吡格雷低反应性与临床缺血事件的发生具有相关性；携带功能减低的CYP2 C19基因型虽然可影响RPA水平，但尚不支持其与临床缺血事件的发生相关。Objective To evaluate the correlation between RPA or the polymorphism of CYP 2C19 and the incidence of ischemic events and the influence on the clinical prognosis .Methods A case-control study was used.A total of 202 patients [male 66%,（63 ±11） years] with ACS on aspirin and clopidogrel treatment were recruited , whose RPA were measured by whole blood aggregometry （ WBA ） , and their CYP2C19 polymorphism were also tested .Their clinical ischemic events were recorded in the mean follow-up period of 16 months.The RPA cut-off values for antiplatelet low-responsiveness were defined by the receiver operator characteristic curve （ ROC）; the relationships of clinical outcomes with RPA and CYP 2C19 were assessed by the Kaplan-Meier survival analysis.Results CYP2C19＊2 （681G〉A） present in 52.5% of recruited patients and＊3 （636G〉A） present in12.9%.RPA induced by adenosine diphosphate （ ADP） showed significant difference among CYP 2C19＊2 or ＊3 heterozygotes, CYP2C19＊2 or ＊3 homozygotes and noncarriers （χ2 =9.318, P=0.009）;whereas, RPA induced by arachidonic acid （AA） （χ^2 =2.441, P=0.295） and the incidence of ischemic events （χ^2 =0.513, P=0.774） were not.During follow-up, 18 （9%） patients experienced clinical ischemic episodes , and their RPA were higher than patients without ischemic episodes [（8.6 ±4.8） Ωvs （5.2 ±3.7） Ω, P =0.013; （8.6 ±6.8） Ωvs （1.6 ±3.7） Ω, P 〈0.001].Moreover, employing 6.5 Ω（induced by ADP） and 2.5 Ω（induced by AA） as cutoff values,RPA showed optimal negative predictive values （97%, 96%） and poor positive predictive values （16%,29%）.Survival analysis showed, statistically, patients with clopidogrel low-responsiveness had higher riskof ischemic episodes than patients with clopidogrel responsiveness （HR =2.86, χ^2 =11.27,P =0.0008）;however, patients with aspirin low responsiveness （HR =1.77, χ^2 =1.74, P =0.19） or patients withCYP2C19＊2 or ＊3 （HR =0.89, χ^2 =0.12, P =0.73） did no

关 键 词：急性冠状动脉综合征 血小板活化 血小板功能试验 

分 类 号：R541.4[医药卫生—心血管疾病] R440[医药卫生—内科学]