The Relationship Study Between Variants Of α-ENaC Gene And Essential Hypertension In Xinjiang Kazakhs

Objective:To investigate the relationship between T663A,G(2139)A,G(3091)A single nucleotide polymorphisms(SNPs)ofα-ENaC gene which located at 13 exon region and promoter region respectively,gene haplotype and essential hypertension in Xinjiang Kazakhs.Methods:More than 500 Xinjiang Kazakhs who lived in pasture area of Hefen,Xinyuan,Fuhai and Fuyun county were recruited in our study.After questionnaire and physical examination,They were divided into hypertensives(EH group) whose SBP≥140mmHg and/or DBP≥90mmHg and normotensives(NT group)whose BP＜140/90mmHg.We measured theirα-ENaC gene T663A,G(2139)A,G(3091)A polymorphisms by PCR-RFLP method and tested the association of the polymorphisms and haplotype with hypertension.Result:1)Three kinds of genotype and two kinds of allele ofα-ENaC gene T663A polymorphism were detected in Xinjiang Kazakhs.In the population,the frequencies of the genotype AA,AG,GG were 15.7%,50.2%,34.1%and the frequencies of allele A,G were 40.7%,59.3%respectively.The genotypic and allelic frequencies were in Hardy-Weinberg equilibrium(x~2=0.78,P=0.37).The distributed frequencies of AA,AG,GG genotype were 16.3%,49.0%,34.6%of hypertensive patients and 15.1%,51.4%,33.6%of controls respectively.The distributed frequencies of A and G allele were 40.8%,59.2%of hypertensive patients and 40.7%,59.3%of controls respectively.The distribution of genotypic and allelic frequencies had no significant difference between EH and NT groups(x~2=0.31,P=0.85;x~2=0.02,P=0.96).Through analyzing the data stratified with gender,BMI,the distribution of genotypic and allelic frequencies had no significant difference between two groups(P＞0.05).In younger subjects,the distribution of genotypic and allelic frequencies had no significant difference between EH and NT groups(P＞0.05).There was no significant difference of blood pressure among subjects with the three kinds of genotype(P＞0.05).Through analyzing the data stratified with gender,BMI,there was no significant difference of blood pressure among subjects with the three kinds of genotype whether male,female or normoweight, overweight(P＞0.05).There was no significant difference of blood pressure among younger subjects with the three kinds of genotype too(P＞0.05).In multiple logistic analysis,the genotype of the T663A polymorphism were excluded as independent variable after controlling the mixed factors of age,gender,BMI.2)We detected three kinds of genotype and two kinds of allele ofα-ENaC gene G(2139)A polymorphism in Xinjiang Kazakhs.The frequencies of the genotype AA,AG,GG were 26.2%,51.6%, 22.2%and the frequencies of allele A,G were 51.9%,48.1%respectively,the genotypic and allelic frequencies were in Hardy-Weinberg equilibrium(x~2=0.60,P=0.43).The distributed frequencies of AA,AG,GG genotype were 24.9%,52.5%,22.6%of hypertensive patients and 26.7%,49.6%,21.1%of controls respectively.The distributed frequencies of A and G allele were 51.1%,48.9%of hypertensive patients and 52.8%, 47.2%of controls respectively.Both of genotypic and allelic frequencies had no significant difference between EH and NT groups(x~2=0.41,P=0.81;x~2=0.30,P=0.58). Through analyzing the data stratified with gender,BMI,the distribution of genotypic and allelic frequencies had no significant difference between two groups(P＞0.05).In younger subjects,the distribution of genotypic and allelic frequencies had no significant difference between EH and NT groups(P＞0.05).There was no significant difference of blood pressure among subjects with the three kinds of genotype.Through analyzing the data stratified with gender,BMI,there was no significant difference of blood pressure among subjects with the three kinds of genotype whether male,female or normoweight, overweight(P＞0.05).In multiple logistic analysis,the genotype of the G(2139)A polymorphism were excluded as independent variable after controlling the mixed factors of age,gender,BMI.3)We detected three kinds of genotype and two kinds of allele ofα-ENaC gene G(3091)A polymorphism in Xinjiang Kazakhs.The frequencies of the genotype AA,AG,GG were 19.6%,52.0%,28.4%and the frequencies of allele A,G were 45.5%,54.5%respectively,the genotypic and allelic frequencies were in Hardy-Weinberg equilibrium(x~2=1.21,P=0.27).The distributed frequencies of AA,AG,GG were 19.7%, 52.1%,28.2%of hypertensive patients and 19.5%,51.9%,28.6%of controls respectively. The distributed frequencies of A and G allele were 45.6%,54.4%of hypertensive patients and 45.4%,54.6%of controls respectively.The distribution of genotypic and allelic frequencies had no significant difference between EH and NT groups(x~2=0.01,P=0.99; x~2=0.03,P=0.95).Through analyzing the data stratified with gender,BMI,age,the distribution of genotypic and allelic frequencies had no significant difference between two groups(P＞0.05).There was no significant difference of blood pressure among subjects with the three kinds of genotype.Through analyzing the data stratified with gender,BMI,there was no significant difference of blood pressure among subjects with the three kinds of genotype whether male,female or normoweight,overweight(P＞0.05). In multiple logistic analysis,the genotype of the G(3091)A polymorphism were excluded as independent variable after controlling the mixed factors of age,gender,BMI.4)Nine kinds of united genotype were composed by two kinds of SNP G(2139)A and G(3091)A, The distribution of the united genotypic frequencies had no significant difference between EH and NT groups(x~2=10.77,P=0.21).5)Eight kinds of haplotype were detected in in Xinjiang Kazakhs.Seven kinds of main haplotype were detected in hypertensives and normotensives respectively,6)There were significant difference of haplotypic frequencies between EH and NT groups.The frequency of haplotype A663-G2139-A3091 of EH group was significant lower than that of NT group,wheras the frequency of haplotype G663-A2139- A3091 of EH group was significant highier than that of NT group(P＜0.05).7)We did not find linkage disequilibrium in three SNPs.Conclusion:1)There existed T663A,G(2139)A,G(3091)A polymorphisms ofα-ENaC gene in Xinjiang Kazakhs.There were three kinds of genotype AA,AG,GG and two kinds of allele A.G of T663A,G(2139)A,G(3091)A polymorphisms.2)The results of our study indicated that T663A,G(2139)A,G(3091)A polymorphisms might not be associated with essential hypertension of Xinjiang Kazakhs.3)The united genotype of G(2139)A and G(3091)A polymorphisms might not be associated with essentiat hypertension of Xinjiang Kazakhs. 4)The haplotype ofα-ENaC gene might be associated with essential hypertension of Xinjiang Kazakhs.The risk of essential hypertension might be decreased by haplotype A663-G2139-A3091,wheras increased by haplotype G663-A2139-A3091.5)The single polymorphism ofα-ENaC gene might not be associated with essential hypertension of Xinjiang Kazakhs,but the blood pressure of Xinjiang Kazakhs might be significantly affected by the haplotype ofα-ENaC gene.