CAJ | 학술논문

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.
목적 분석대양린매1 (paraoxonase 1,PON1)기인다태성여복용록필격뢰후졸중재발지간적상관성.방법 종남경졸중주책계통중제취2008년5월지2010년4월수발결혈성졸중병장기복용록필격뢰적환자.채용개량적다중고온련접매검측반응기술대입선병례적PON1Q192R、PON1 L55M적단핵감산기인다태성위점진행기인분형병수방,수방적주요종점사건포괄결혈성뇌혈관사건、심기경사、혈관성사망;차요종점사건포괄출혈성혈관사건.채용잡보란-매야생존분석법탐토불동기인형환자종점사건적차이성.용단인소、다인소COX회귀모형분석림상종점사건발생적상관위험인소.결과 공입조환자625례,평균수방기시간위(12.7±5.1)개월,기주요종점사건적발생솔위13.6％ (85/625),기중재발졸중65례(10.4％),혈관성사망13례(2.1％),심기경사7례(1.1％).출혈성사건발생13례(2.1％).PON1Q192R화PON 1L55M적최소등위기인빈솔분별위38.1％(238/625)화2.8％(17.5/625).휴대QQ/QR적환자주요림상종점사건발생62례(15.7％),비휴대자(RR)적주요종점사건발생23례(10.0％),조간차이유통계학의의(HR=1.68,95％ CI1.04～2.71,P=0.030).다인소COX회귀모형납입년령、성별、체중지수、고혈압、당뇨병、고지혈증、관상동맥죽양경화심장병사、흡연이급합병약물위상관위험인소,분석결과현시:PON1Q192기인형여결혈성졸중환자재발구유일정적상관성(HR =2.39,95％ CI 1.33 ～4.29,P=0.004).결론 재장기복용록필격뢰항혈소판치료적결혈성졸중환자중,PON1 Q192기인형휴대자재발결혈성뇌혈관사건적풍험명현증고,다인소분석제시PON1 Q192기인형여결혈성뇌혈관병환자재발구유일정상관성.
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.