Association study between WNK1 gene polymorphisms and ischemic stroke in Uygur

Abstract

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 ischemic 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, χ2-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%CI 0.269—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. Key words: Protein-serine-threonine kinases; Brain ischemia; Stroke; Polymorphism; single nucleotide; Uygur nationality