血红素加氧酶1基因rs2071746多态性与缺血性卒中患者远期转归的相关性  

Correlation between heme oxygenase-1 gene rs2071746 polymorphism and long outcome in patients with ischemic stroke

作　　者：曹立平 朱林凤[1] 李华杰[1] 季蕾[1] 岳春贤 吴坚[1] 盛世英[1] 练学淦[1] Cao Liping;Zhu Linfeng;Li Huajie;Ji Lei;Yue Chunxian;Wu Jian;Sheng Shiying;Lian Xuegan(Department of Neurology,the Third Affiliated Hospital of Soochow University,Changzhou 213000,China)

机构地区：[1]苏州大学附属第三医院神经内科,常州213000

出　　处：《国际脑血管病杂志》2019年第5期343-347,共5页International Journal of Cerebrovascular Diseases

基　　金：常州市卫计委指导性课题(WZ201508).

摘　　要：目的探讨血红素加氧酶1(heme oxygenase-1,HO-1)基因rs2071746多态性与缺血性卒中远期临床转归的相关性。方法连续纳入2015年7月至2017年6月期间苏州大学附属第三医院神经内科收治的急性缺血性卒中患者,并对所有患者进行TOAST分型。应用改良多重连接酶检测反应技术进行HO-1基因rs2071746多态性基因型分型。对患者进行临床随访,主要终点事件包括缺血性卒中、血管性死亡和心肌梗死。应用多因素Cox比例风险回归模型分析主要终点事件的独立影响因素.结果共纳入1698例基因分型成功并获得随访信息的患者。基因分型表明,rs2071746A等位基因频率为44.91%。随访(15.21±7.39)个月,168例(9.89%)患者发生主要终点事件。A等位基因携带者主要终点事件发生率显著低于非A等位基因携带者(8.80%对12.40%;P=0.018)。多变量Cox比例风险回归模型显示,在校正年龄、性别、高血压、糖尿病、既往卒中或短暂性脑缺血发作史、吸烟、饮酒及基因型后,A等位基因是急性缺血性卒中患者发生主要终点事件的独立保护因素[风险比(hazard risk,HR)0.693,95%可信区间(confidence interval,CI)0.506~0.949;P=0.022]。亚组分析显示,携带A等位基因是大动脉粥样硬化性卒中患者发生主要终点事件的独立保护因素(HR 0.651,95%CI 0.425~0.997;P=0.048),而在其他病因学亚型中未显示rs2071746多态性与远期转归存在联系。结论HO-1基因rs2071746 A等位基因可能是急性缺血性卒中及大动脉粥样硬化性卒中患者远期转归的保护因素。Objective To investigate the association between heme oxygenase-1(HO-1)gene rs2071746 polymorphism and long-term clinical outcome in patients with ischemic stroke.Methods Between July 2015 and June 2017,consecutive patients with acute ischemic stroke admitted to the Department of Neurology,the Third Affiliated Hospital of Soochow University were enrolled prospectively.TOAST classification was performed for all patients.Genotyping of the HO-1 gene rs2071746 polymorphism was performed using a modified multiplex ligase detection reaction technique.The patients were followed up.The primary endpoint events included ischemic stroke,vascular death,and myocardial infarction.Multivariate Cox proportional hazard regression model was used to analyze the independent influencing factors for primary endpoint events.Results A total of 1 698 patients with successful genotyping and follow-up information were enrolled.Genotyping showed that the frequency of rs2071746 A allele was 44.91%.They were followed up for 15.21±7.39 months,and 168 patients(9.89%)had primary endpoint events.The incidence of primary endpoint events in A allele carriers was significantly lower than that in non-A allele carriers(8.80%vs.12.40%;P=0.018).Multivariate Cox proportional risk regression model showed that after adjusting for age,gender,hypertension,diabetes mellitus,smoking,alcohol consumption,and genotype,A allele was an independent protective factor for primary endpoint events in patients with acute ischemic stroke(hazard risk[HR]0.693,95%confidence interval[CI]0.506-0.949;P=0.022).Subgroup analysis showed that carrying the A allele was an independent protective factor for primary endpoint events in patients with large atherosclerotic stroke(HR 0.651,95%CI 0.425-0.997;P=0.048),while rs2071746 polymorphism was not associated with long-term outcome in other etiological subtypes.Conclusion The HO-1 gene rs2071746 A aDele may be a protective factor for the long-term outcome in patients with acute ischemic stroke and large atherosclerotic stroke.

关 键 词：卒中 脑缺血 血红素加氧酶-1 多态现象 遗传学 预后 危险因素 

分 类 号：R743.3[医药卫生—神经病学与精神病学]