血红素加氧酶1基因多态性与老年缺血性卒中预后的关系

Correlation between heme oxygenase-1 gene polymorphisms and prognosis of ischemic stroke in elderly patients

目的探讨血红素加氧酶1（HO-1）基因rs2071746（T-413A）位点多态性与老年缺血性卒中患者预后的相关性。方法采用前瞻性队列研究，纳入2009年12月-2012年10月在南京卒中注册系统中年龄≥60岁的缺血性卒中患者。按急性卒中治疗org10172试验（TOAST）分型对患者分类。采用改良多重连接酶反应技术进行基因分型。患者出院后3、6、12、24个月进行随访，主要终点事件为血管性疾病导致的死亡、非致死性缺血性卒中及心肌梗死。结果①共有961例患者入组，TT型295例，TA型459例，AA型207。随访（15．0±7．4）个月，114例（11．9％）患者发生主要终点事件，其中TT型44例，TA型47例，AA型23例。@rs2071746位点A等位基因频率为45．4％。显性遗传模式显示，携带变异基因（AA＋AT型）患者比非携带变异基因（TT型）患者终点事件发生率低[分别为10．5％（70/666）与14．9％（44/295）]，差异有统计学意义（HR=0．67，95％C1：0．46～0．97，P=0．034）。多因素Cox回归分析调整混杂因素后，携带rs2071746位点A基因是缺血性卒中预后的保护因素（HR=0．67，95％CI：0．45-0．99，P=0．043）。③对卒中亚型分析发现，大动脉粥样硬化性卒中患者中，AA＋AT基因型患者终点事件发生率较TT型患者低（HR=0．56，95％CI：0．33～0．94，P=0．028）；其他亚型的基因型与终点事件发生率无相关性。结论HO-1基因rs2071746位点A等位基因可能是老年缺血性卒中及其大动脉粥样硬化性卒中患者预后的保护性因素。

Objective To investigate the correlation between heme oxygenase-1 （HO-1） gene rs2071746 （T-413A） polymorphisms and the prognosis in elderly patients with ischemic stroke. Methods Consecutive patients with isehemie stroke aged I〉 60 years from Nanjing Stroke Registry Program （NSRP） from December 2009 to October 2012 were enrolled into this prospective cohort study. The patients were classified according to TOAST classification. The improved multiple ligase detection reaction was used for genotyping. The patients were followed up at 3, 6, 12, and 24 months after discharge from hospitals. The primary outcome endpoints were death, nonfatal ischemic stroke, and myocardial infarction resulted from vascular diseases Results ①A total of 961 patients were enrolled, from which 295 were TT genotypes, 459 were TA genotypes, and 207 were AA genotypes. After an average of 15.0 ± 7.4 months follow-up, 114 patients （11.9% ） had the primary outcome endpoints, of which 44 patients were TT genotypes, 47 were TA genotypes, and 23 were AA genotypes. ② The frequency of rs2071746 A allele locus was 45.42%. The autosomal dominant mode showed that the primary outcome endpoint rate in patients carryingmutated genes （ AA ＋ AT genotypes） was lower than that in patients without carrying mutated genes （ TT genotypes） （10.5% [70/666] vs. 14.9% [44/295 ] ） with significant difference （HR = 0.67, 95% CI 0.46 -0.97, P = 0. 034 ]. After adjustment for the confounding factors, the multivariate Cox regression analysis showed that rs2071746 locus A allele was a protective factor for the prognosis of ischemic stroke （HR =0.67, 95% CI O. 45 -0.99,P = 0. 043）. ③An analysis of stroke subtypes found that the rate of primary outcome endpoint patients with AA ＋ AT genotype was lower than that with Tr genotype for large artery atherosclerotic stroke （ HR = 0.56, 95% C10. 33 -0.94, P = 0. 028 ） , there were no correlation between the genotypes of other subtypes and the rate of primary outcome endpoint. Conclusion A allele of rs2071746 in HO-1 gene may be a protective factor for elderly patients with ischemic stroke and its subtype with large artery atherosclerotic stroke.