The Association Studies Of Xinjiang Uygur, Han Ischemic Stroke Risk Factors Associated With WNK1Gene Polymorphism

Objective:To investigate the distribution differences and risk factors for ischemic stroke between Xinjiang Han and Uygur nationality. Clarifing the relations between lysine-deficient protein kinase1(WNK1) gene single nucleotide polymorphisms and Uygur, Han ischemic stroke, exploring the interaction between WNK1gene polymorphisms and the risk factors.Methods:We conducted standard field epidemiological investigation on Uygur and Han ischemic stroke patients and control subjects from Department of Neurology of5hospitals in Xinjiang. Analyzing the distribution differences of the relative environmental risk factors in the two nationalities and different regions. According to theory of linkage disequilibrium, We genotyped10tagging single nucleotide polymorphisms (tSNPs) of the WNK1gene and examined the WNK1gene polymorphisms of the subjects. The10tSNPs were rs3858703, rs11611246, rs7305065, rs1990021, rs34408667, rs12309274, rs1012729, rs956868, rs12828016and rs953361. Genotyping of them were determined by the Multiplex SNaPshot platform. We studied the effect of each tSNPs and risk factor on ischemic stroke by Logistic regression analysis and deduced the significative haplotypes by Haploview4.2software. To explore the role of WNK1gene polymer-phisms in the pathogenesis of ischemic stroke, we used modern statistical analysis, including stratification analysis, Logistic regression analysis. WNK1-rs11611246was the positive locus we found. The effect of interaction between WNK1-rs11611246genetic polymorphisms and environmental exposures on ischemic stroke was investigated.Results:1) There exist differences of environmental risk factors between the Han and Uygur. Attack rates for ischemic stroke of Han patients with hyperlipidemia, diabetes mellitus, hypertension and drinking were significantly higher than the health people,3.620,3.438,3.015and2.591times respectively (P＜0.001). The detection rates of Uygur ischemic stroke patients with hypertension, diabetes mellitus, and hyperlipidemia were markedly higher than control group (P<0.01),3.678,2.050and1.052times respectively. And drinking, waistline, BMI and age were also associated with ischemic stroke in Uygur. Their OR were2.625,1.977、1.950、1.032respectively (P<0.05).2) There were no statistical significance of discrepancies of waistline, hypertension, diabetes mellitus, hyperlipidemia, stroke recurrence and family history of cardio-cerebrovascular diseases between Han and Uygur ischemic stroke patients (P>0.05). The rates of smoking and drinking of Han patients were higher than Uygur ones (P<0.05). The rate of smoking of Uygur and Han patients were31.5%and37.1%(P=0.026). The BMI of Uygur patients was higher than Han ones (P=0.012). No statistical significance of discrepancies of NIHSS scores and TAOST classification were found between two nationalities.3) The waistline of northern Han and Uygur ischemic stroke patients was higher than southern ones (P=0.001). The detection rates of northern Han ischemic stroke patients with excessive drinking and hypertension were markedly higher than southern Han ones (P<0.01).4) Association analysis of WNK1gene and ischemic stroke:WNK1-rs11611246was associated with the incidence of ischemic stroke in Uygur and Han, with the OR0.730and0.760respectively. When further stratifying the samples according to gender, we found that T allele was associated with a reduced risk of ischemic stroke in female Uygur and male Han,0.534and0.702times of the control group respectively. The significance remained after adjustment for the covariates of age (P<0.05), and for the covariates of age, BMI, cigarette smoking, alcohol drinking, hypertension, diabetes and hyperlipidemia (P<0.05).5) There existed the interaction between the risk factors (hypertension, diabetes) and rs11611246. The risk of hypertension patients without GT/TT gene suffering from ischemic stroke was3.149times of health people, while the risk was2.093times of ones with GT/TT gene. The risk of male Han diabetes patients with GT/TT gene suffering from ischemic stroke was down-regulated frome3.122times to2.973times. And the risk of female Uygur diabetes patients with GT/TT gene suffering from ischemic stroke was down-regulated frome4.636times to2.375times.Conclusions:1) There were significant differences of risk factors for ischemic stroke in Xinjiang resulting from the national and regional disparity. The risk factors of ischemic stroke in Han are hyperlipidemia, diabetic mellitus, hypertension and excessive drinking, while in Uygur are:hypertension, diabetic mellitus, hyperlipoidemia, age, BMI, waistline and excessive drinking. The rate of Uygur and Han patients with central adiposity in northern Xinjiang was higher than in the southern part. The rates of excessive drinking and hypertension of Han ischemic stroke patients in sourthern Xinjiang was higher, and no significant differences were found of Uygur ones between sourthern and northern parts.2) WNK1gene was associated with ischemic stroke. The T allele was the protecting factor of ischemic stroke in male Han and female Uygur ischemic stroke patients.3) There existed negative interaction between T allele with hypertension and diabetes. The risk of patients with hypertensive and diabetic suffering from ischemic stroke can be reduced in male Han and female Uygur.