PDE4D基因SNP83多态性与缺血性卒中预后的相关性研究

摘要

Objective To investigate the association between single nucleotide polymorphism 83 (SNP83) polymorphism in phosphodiesterase 4D (PDE4D) gene and prognosis of ischemic stroke. n Methods We consecutively enrolled 736 ischemic stroke patients who admitted to Beijing Tiantan Hospital from October 2009 to July 2011, andSNP83 was genotyped by the Sequenom Massyarray technique. Logistic regression analysis was used to investigate the association betweenSNP83 and three months' prognosis of ischemic stroke under different genetic models. Combined endpoint event was defined as recurrence of stroke, death of all causes and other cerebro-cardiovascular events. n Results A total of 736 ischemic stroke patients were enrolled into the study, and 677 patients had information of follow-up after three months of stroke. Compared with the patients without combined endpoint event, the patients with combined endpoint event were older ([67.02±0.70] vs [59.98±3.35],P<0.001), had higher proportion of history of atrial fibrillation (9.3%vs 3.7%, P=0.048), and had higher National Institutes of Health Stroke Scale (NIHSS) score[11(5~16) vs 5(2~9),P<0.001]. When analyzing the gene polymorphism, we found that the proportion of AG+GG genotype was signiifcantly higher in the patients with combined endpoint event than those without combined endpoint event (50.0%vs 36.7%,P=0.007), and in the multivariable analyzing adjusted for age, NIHSS score and history of atrial ifbrillation, theAG/GG genotype was signiifcantly associated with combined endpoint event (adjusted odds ratio [OR] 1.84, 95% conifdence interval [CI] 1.04~3.26). However, no signiifcant association was found with poor outcome after ischemic stroke. n ConclusionAG/GG genotype ofSNP83 inPDE4D gene was associated with combined endpoint event after ischemic stroke.%目的探索磷酸二酯酶4D（phosphodiesterase 4D，PDE4D）基因的基因多态性（single nucleotide polymorphism，SNP）83（rs966221）与缺血性卒中预后的相关性。n　　方法连续入组2009年10月～2011年7月北京天坛医院神经内科住院的缺血性卒中患者736例，采用Sequenom Massyarray技术检测SNP83位点基因分布情况。采用Logistic回归模型分析不同遗传模型下该位点基因多态性与卒中后3个月联合终点事件（包括卒中复发、死亡和其他血管事件等）和预后不良[改良Rankin量表（modified Rankin Scale，mRS）评分＞1]的相关性，并对卒中亚型进行分层分析。n　　结果本研究共纳入736例患者，其中677例患者完成3个月的随访，失访率为8.02%。与未发生联合终点事件组的患者相比，发生联合终点事件组的患者年龄较大[（67.02±0.70）vs （59.98±3.35）， P＜0.001]，既往心房颤动病史比例较高（9.3%vs 3.7%，P=0.048），入院时美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale，NIHSS）评分较高[11（5～16）vs 5（2～9），P＜0.001]，且差异具有显著性，而两组的其他基线信息（如性别、民族、婚姻状况、居住方式、既往吸烟、饮酒、高血压、糖尿病、高脂血症和冠状动脉粥样硬化性心脏病等）差异无显著性（P＞0.05）。进行基因多态性分析发现，与未发生联合终点事件患者相比，发生联合终点事件患者中SNP83 AG+GG基因型的比例较高（50.0%vs 36.7%，P=0.007），调整年龄、入院时NIHSS评分和既往心房颤动病史，Logistic回归分析显示该位点在显性模型（AG+GG vs AA）下与缺血性卒中后联合终点事件发生相关[调整后的比值比（odds ratio，OR）1.84，95%可信区间（confidence interval，CI）1.04～3.26]，但并未发现该位点与卒中预后不良相关。n　　结论 PDE4D基因SNP83AG/GG基因型与缺血性卒中后联合终点事件发生相关。