中文摘要：

目的探索赖氨酸蛋白缺乏激酶1（with no lysine[K]1，WNK1）基因单核苷酸多态性（SNP）与中国维吾尔族缺血性卒中的关系。方法收集295例维吾尔族缺血性卒中患者和318例其他疾病对照者，进行病例对照研究。用标签SNP（tagging—SNP，tSNP）策略选择WNK1基因10个SNP位点（rs3858703、rs11611246、rs7305065、rs1990021、rs34408667、rs12309274、rs1012729、rs956868、rs12828016、rs953361）。SNPs基因分型检测采用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rs11611246位点T等位基因在对照组中的分布（30．0％）高于病例组（25．6％），但是差异无统计学意义。用性别进一步分层分析，发现rs11611246T等位基因是维吾尔族女性卒中发病的保护因子。显性遗传模型显示T等位基因携带者发生缺血性卒中的风险是对照组的0．448倍（95％CI0．269—0．746，P=0．002）。调整年龄后差异仍有统计学意义，进一步调整混杂因素年龄、体质量指数、吸烟、饮酒、高血压、糖尿病、高脂血症后，差异仍有统计学意义。除此之外，WNK1基因其余9个SNPs位点未发现同维吾尔族人脑梗死相关。结论我们首次发现WNK1基因第4内含子rs11611246多态影响缺血性卒中的发生，rs11611246位点T等位基因可能是维吾尔族女性发生缺血性卒中的保护因素。

英文摘要：

Objective To explore the association between single nucleotide polymorphisms （SNPs） in WNK1 gene and ischemic stroke in Uygur population. Methods Ten tagging single nucleotide polymorphisms （tSNPs） of the WNK1 gene in 295 ischemic stroke patients and 318 control subjects were genotyped, and the association between these tSNPs and isehemic stroke were conducted. The 10 tSNPs were rs3858703, rs11611246, rs7305065, rs1990021, rs34408667, rs12309274, rs1012729, rs956868, rs12828016 and rs953361. They were determined by the Multiplex SNaPshot platform. All data were analyzed using t-test, X2-test and Logistic regression. Linkage disequilibrium and Haplotype were analyzed by Haploview software. Results There were no significant differences between cases （25.6%） and controls （30. 0% ） of the 10 tSNPs in WNK1 gene. When the samples were further stratified according to gender, rs11611246 T allele was found to be associated with a reduced risk of ischemic stroke, with a per-allele OR of 0. 448 （ 95% CI0. 269--0. 746, P = 0. 002 ） in female cases than in female controls. The significance remained after adjustment for the covariates of age, and for the covariates of age, BMI, cigarette smoking, alcohol drinking, hypertension, diabetes and hyperlipidemia. In addition, no association between the other 9 tSNPs and ischemic stroke were found in Uygur subjects. Conclusion The study reports a new genetic variant, rs11611246, located in the fourth intron of the WNK1 gene, decreasing the risk of ischemic stroke in Uygur population. The T allele might be the protecting factor of ischemic stroke in female Uygur.