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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org 10172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。②rs2071746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%CI: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 relationship between rs2071746 (T-413A) polymorphism of heme oxygenase 1 (HO-1) gene and the prognosis of elderly patients with ischemic stroke. Methods A prospective cohort study was conducted in patients with ischemic stroke aged 60 years and older in the Nanjing Stroke Registration System from December 2009 to October 2012. Patients were classified according to the acute stroke treatment org 10172 test (TOAST) classification. Genotyping was performed using a modified multiplex ligase reaction technique. Patients were followed up 3, 6, 12, and 24 months after discharge. The primary endpoint was death from vascular disease, nonfatal ischemic stroke, and myocardial infarction. Results ① A total of 961 patients were enrolled. There were 295 TT patients, 459 TA patients and 207 AA patients. A total of 114 patients (11.9%) had a primary endpoint of follow-up (15.0 ± 7.4) months, of whom 44 were TT, 47 were TA, and 23 were AA. ② rs2071746 locus A allele frequency was 45.4%. The dominant genetic pattern showed a lower prevalence of endpoints in patients with variant gene (AA + AT type) than in non-variant gene (TT type) [10.5% (70/666) vs 14.9% (44/295, respectively] , The difference was statistically significant (HR = 0.67, 95% CI: 0.46 ~ 0.97, P = 0.034). Multivariate Cox regression analysis showed that carrying rs2071746 A gene was a protective factor in prognosis of ischemic stroke (HR = 0.67, 95% CI: 0.45-0.99, P = 0.043) after adjusting for confounding factors. (3) Analysis of stroke subtypes showed that the incidence of end point events was higher in AA patients with atherosclerotic stroke than in TT patients (HR = 0.56, 95% CI: 0.33-0.94, P = 0.028). The genotypes of other subtypes did not correlate with the incidence of endpoint events. Conclusion A allele of rs2071746 HO-1 gene may be a protective factor in the prognosis of elderly patients with ischemic stroke and its large atherosclerotic stroke.