【摘要】 目的:探索赖氨酸缺乏蛋白激酶1(Wnk1)基因单核苷酸多态性(SNP)与中国汉族人群缺血性卒中的关系。方法:收集2008年1月~2009年12月新疆5所医院294例汉族缺血性卒中患者(病例组)和同期外科系统住院治疗的其他无脑梗死疾病的汉族患者314例(对照组)进行病例对照研究。用标签SNP(tSNP)策略选择Wnk1基因10个SNP位点(rs3858703、rs11611246、rs7305065、rs1990021、rs34408667、rs12309274、rs1012729、rs956868、rs12828016、rs953361)。SNP基因分型检测采用多重SNaPshot平台。用t检验、卡方检验和logistic回归分析对数据进行统计分析,用Haploview软件进行连锁不平衡分析和单倍型分析。结果:病例组饮酒(37.1%)、高血压病(62.9%)、糖尿病(18.0%)、高脂血症(36.4%)患者比例均高于对照组(均P<0.01),而吸烟者比例在两组间差异无统计学意义(P>0.05)。所有位点基因分型缺失率均在1%以下。除rs34408667位点外,其余tSNP均通过Hardy-Weinberg平衡检验。Wnk1基因第四内含子rs11611246位点与汉族缺血性卒中相关。T等位基因在病例组中的分布频率低于对照组(30.3%与35.7%,P=0.046)。进行性别分层后发现,rs11611246 T等位基因是汉族男性缺血性卒中发病的保护因子。GT基因型及TT基因型在病例组男性中的分布频率分别为43.3%及7.2%,而在对照组男性中的分布频率分别为43.1%及15.2%(P=0.038)。加性遗传模型显示T等位基因携带者发生缺血性卒中的风险是对照组的0.702倍(95%CI:0.517~0.953,P=0.023)。调整年龄后差异仍然存在(P=0.022),进一步调整年龄、体质量指数、吸烟、饮酒、高血压、糖尿病、高脂血症等混杂因素后,差异仍然存在(P=0.008)。未发现Wnk1基因其余9个SNP位点与汉族人脑梗死相关。结论:Wnk1基因第四内含子rs11611246多态性影响中国人缺血性卒中的发生。rs11611246位点T等位基因可能是汉族男性发生缺血性卒中的保护因素。更多还原

【Abstract】 Objective: To investigate the association between single nucleotide polymorphisms( SNPs) in Wnk1 gene and ischemic stroke in Chinese Han population. Methods: A hospital-based case-control study was carried out. The ischemic stroke group included 294 Chinese Han subjects,who were admitted with non-fatal ischemic stroke in departments of neurology of 5 hospitals in Xinjiang during January 2008 through December 2009. Control group included 314 age and sex-matched Han subjects without an inquired history of stroke,hospitalized in departments of surgery of these 5 hospitals. Ten tagging SNPs( tSNPs) of the Wnk1 gene were genotyped,and the association between these tSNPs and ischemic stroke were evaluated. The tSNPs( rs3858703,rs11611246,rs7305065,rs1990021,rs34408667,rs12309274,rs1012729,rs956868,rs12828016 and rs953361) were determined by the Multiplex SNaPshot platform. The data were analyzed by using t-test,χ2-test and logistic regression. Linkage disequilibrium and haplotype were analyzed by Haploview software. Results: The rates of alcohol drinking,hypertension,diabetes and hyperlipidemia in ischemic stroke group were higher than those in control group( 37. 1% vs 21. 0%,62. 9% vs 36. 6%,18. 0% vs 6. 1% and 36. 4% vs 17. 5%,respectively,all P < 0. 01). No significant difference in smoking rate was found between two groups. The genotyping loss rates of all sites were less than 1%. All the tSNPs were examined by Hardy-Weinberg equilibrium test except rs34408667. tSNP rs11611246 in the 4th intron of the Wnk1 gene was significantly associated with ischemic stroke. The distribution frequency of T allele in cases was significantly lower than that in male controls( 30. 3% vs 35. 7%,P = 0. 046). When the samples were further stratified according to gender,rs11611246 was found to be associated with a reduced risk of ischemic stroke in male cases than in controls. GT and TT genotype frequencies were 43. 3% and 7. 2% in male cases,43. 1% and 15. 2% in male controls,respectively( P = 0. 038). The T allele was associated with a reduced risk of ischemic stroke,with a per-allele OR of 0. 702( 95% CI: 0. 517-0. 953,P = 0. 023) in male cases than in male controls. The significance remained after adjusting the covariates of age( P = 0. 022),or the covariates of age,BMI,cigarette smoking,alcohol drinking,hypertension,diabetes and hyperlipidemia( P = 0. 008). No association between other 9 tSNPs and ischemic stroke was noted in Chinese Han subjects. Conclusion: The polymorphism of rs11611246 on the 4th intron of Wnk1 gene is associated with a reduced risk of ischemic stroke in Chinese Han population and the T allele might be a protective factor for ischemic stroke in male Chinese Hans.更多还原