中文摘要：

目的 分析对氧磷酶1 （paraoxonase 1,PON1）基因多态性与服用氯吡格雷后卒中再发之间的相关性.方法 从南京卒中注册系统中提取2008年5月至2010年4月首发缺血性卒中并长期服用氯吡格雷的患者.采用改良的多重高温连接酶检测反应技术对入选病例的PON1Q192R、PON1 L55M的单核苷酸基因多态性位点进行基因分型并随访,随访的主要终点事件包括缺血性脑血管事件、心肌梗死、血管性死亡;次要终点事件包括出血性血管事件.采用卡普兰-迈耶生存分析法探讨不同基因型患者终点事件的差异性.用单因素、多因素COX回归模型分析临床终点事件发生的相关危险因素.结果 共入组患者625例,平均随访期时间为（12.7±5.1）个月,其主要终点事件的发生率为13.6％ （85/625）,其中再发卒中65例（10.4％）,血管性死亡13例（2.1％）,心肌梗死7例（1.1％）.出血性事件发生13例（2.1％）.PON1Q192R和PON 1L55M的最小等位基因频率分别为38.1％（238/625）和2.8％（17.5/625）.携带QQ/QR的患者主要临床终点事件发生62例（15.7％）,非携带者（RR）的主要终点事件发生23例（10.0％）,组间差异有统计学意义（HR=1.68,95％ CI1.04～2.71,P=0.030）.多因素COX回归模型纳入年龄、性别、体重指数、高血压、糖尿病、高脂血症、冠状动脉粥样硬化心脏病史、吸烟以及合并药物为相关危险因素,分析结果显示：PON1Q192基因型与缺血性卒中患者再发具有一定的相关性（HR =2.39,95％ CI 1.33 ～4.29,P=0.004）.结论 在长期服用氯吡格雷抗血小板治疗的缺血性卒中患者中,PON1 Q192基因型携带者再发缺血性脑血管事件的风险明显增高,多因素分析提示PON1 Q192基因型与缺血性脑血管病患者再发具有一定相关性.

英文摘要：

Objective To investigate the impact of paraoxonase 1 （PON1） Q192R as well as L55M genotypes on the risk of recurrent ischemic events in a cohort of Chinese patients treated with clopidogrel.Methods Consecutive patients with ischemic stroke registered in Nanjing Stroke Registry Program between May 2008 and April 2010 were enrolled in this study.Single-nucleotide polymorphisms genotyped included PON1Q192R,PON1L55M.Genotypes were determined by improved multiple ligase detection reaction.All patients were genotyped and clinical outcomes were determined with three monthly follow-up.The primary endpoint was a composite of vascular death,and nonfatal ischemic stroke and myocardial infarction and secondary endpoint was bleeding events.Cumulative risk of primary endpoint according to genotypes was presented with Kaplan-Meier survival curve.Differences between genotypes in respect to clinical events were assessed by univariate and multivariable Cox proportional-hazards model.Results Of the enrolled 625 patients,during the mean follow-up of （12.7 ± 5.1） months,vascular death was observed in 13 （2.1％）,non-fatal ischemic stroke in 65 （10.4％）,and non-fatal myocardial infarction in 7 （1.1％） patients.The overall primary endpoint was observed in 85 （13.6％） patients.Bleeding events were found in 13 （1.2％） patients.Frequencies of PON1Q192 and PON155M alleles were 38.1％ （238/ 625） and 2.8％ （17.5/325）,respectively.Primary endpoint was observed in 62 （15.7％） of 394 patients with QQ/QR,in 23 （10.0％） of 231 patients with RR during follow-up.PON1Q192 alleles were associated with increased risk of adverse clinical events （HR =1.68,95％ CI 1.04-2.71,P =0.030）.Adjusting for age,sex,and major cardiovascular risk factors,PON1Q192 alleles carriage was independently associated with stroke recurrence （HR =2.39,95％ CI 1.33-4.29,P =0.004）.No relationship between PON1L55M genetic polymorphisms and clinical outcomes was detected.Conclusions PON1Q192R polymorphisms may be deter