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.
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 determinants of clinical efficacy of clopidogrel in ischemic stroke patients in China.A worse clinical outcome occurred in patients carrying PON1Q192 who were treated with clopidogrel after ischemic stroke.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2015年第1期13-17,共5页
Chinese Journal of Neurology
基金
国家自然科学基金资助项目（81070922）
江苏省自然科学基金资助项目（BK2011021）
江苏省“333工程”培养资金资助项目
关键词
脑缺血
卒中
芳基二烷基磷酸酶
噻氯匹定
多态性
单核苷酸
Brain ischemia
Stroke
Aryldialkylphosphatase
Ticlopidine
Polymorphism,single nucleotide
