| Objective: To investigate distributed characteristic of the T3593C, T663A, G2139A, G3091A single nucleotide polymorphisms (SNPs) ofαENaC gene which located at the second intron, the 13th exon region and the promoter region in a subunit gene of epithelial sodium channel (ENaC), respectively, the united genotypes of T3593C and T663A and the haplotypes composed by the G2139A, T663A, G3091A T3593C in Xinjiang Kazakhs. And to research the relationship between four SNPs and the united genotypes with essential hypertension (EH) and serum electrolytes and the association between the haplotypes with EH of Xinjiang Kazakhs. Methods: More than 500 Xinjiang Kazakhs aged more than 30 years old were recruited in this population based on case-control study by cluster sampling who lived in pasture area of Hefen, Xinyuan, Fuhai and Fuyun county in Xinjiang. After questionnaire and physical examination, they were divided into hypertensives (EH group) whose systolic blood pressure (SBP) were≥140mmHg and/or diastolic blood pressure (DBP) were≥90mmHg and normotensives (NT group) whose blood pressure were < 140/90mmHg according to the guideline of the hypertensive prevention and treatment of China in 2005. We extracted the genome DNA of peripheral leucocyte by kits and measured their gene polymorphisms of T3593C, T663A, G2139A, G3091A by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) method. We studied the relationship of the polymorphisms and the united genotypes with EH and serum electrolytes and researched the association of the haplotypes with EH by SPSS 15.0 statistic software and SNPalyze software.Results:1) Three kinds of genotypes and two kinds of alleles of aENaC gene T3593C polymorphism were detected in Xinjiang Kazakhs. In this population, the frequencies of the genotypes TT, TC, CC were 88.39%, 10.63%, 0.98% and the frequencies of alleles T, C were 93.7%, 6.3%, respectively. The genotypic frequencies were in Hardy-Weinberg equilibrium (x~2=5.03, P=0.08). The distributed genotypic frequencies of TT, TC, CC were 89.33%, 9.88%, 0.79% in EH group and 87.45%, 11.37%, 1.18% in NT group, respectively. The distributed allelic frequencies of T, C were 94.36%, 5.64% in EH group and 93.14%, 6.86% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between EH group and NH group (x~2=0.51, P=0.78; x~2=0.55, P=0.46). Through to analyze the data stratified with gender (male and female), BMI (normoweight: BMI<24Kg/m~2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between two groups (P> 0.05). There was no significant difference in levels of blood pressure and serum electrolytes between subjects with the TT and TC+CC genotypes (P>0.05). The genotypes of the T3593C polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes of subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 2) We detected three kinds of genotypes and two kinds of alleles of aENaC gene T663 A polymorphism in Xinjiang Kazakhs. The genotypic frequencies of the AA, AG, GG were 15.7%, 50.2%, 34.1% and the allelic frequencies of A, G were 40.8%, 59.2%, respectively. The distributed genotypic frequencies were in Hardy-Weinberg equilibrium ( x~2 =0.79, P=0.67). The distributed genotypic frequencies of AA, AG, GG were 16.3%, 49.1%, 34.6% in EH group and 15.1%, 51.4%, 33.5% in NT group, respectively. The distributed allelic frequencies of A, G were 40.9%, 59.1% in EH group and 41%, 59% in NT group, respectively. Both of genotypic and allelic frequencies had no significant difference between EH group and NH group (x~2 =0.315, P=0.854; x~2 =0.002, P=1.0). Through to analyze the data stratified with gender (male and female), BMI (normoweight: BMK 24Kg/m~2 ; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between two groups (P>0.05). There was no significant difference in level of blood pressure among subjects with the three kinds of genotypes (P>0.05). But the serum Na~+ of the subjects with AA genotype was higher than those subjects with AG and GG genotypes (P=0.032). The genotypes of the T663A polymorphism were excluded as independent variables relating to EH after controlling the mixed factors of age, gender, BMI by multiple logistic analysis. 3) We detected three kinds of genotypes and two kinds of alleles of G2139A polymorphism in Xinjiang Kazakhs. The genotypic frequencies of AA, AG, GG were 25.88%, 51.95%, 22.17% and the allelic frequencies of A, G were 51.85%, 48.15%, respectively. The genotypic frequencies were in Hardy-Weinberg equilibrium (x~2 =0.84, P=0.66). The distributed genotypic frequencies of AA, AG, GG were 25.1%, 52.1%, 22.8% in EH group and 26.70%, 51.8%, 21.6% in NT group, respectively. The distributed allelic frequencies of A, G were 51.16%, 48.84% in EH group and 52.55%, 47.45% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between these two groups (x~2 =0.211, P=0.900; x~2 =0.199, P=0.663) ). Through to analyze the data stratified with gender (male and female ), BMI (normoweight: BMK24Kg/m2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between these two groups (P>0.05). The genotypes of the G2139A polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes among subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 4) We detected three kinds of genotypes and two kinds of alleles of G3091A polymorphism in Xinjiang Kazakhs. The frequencies of the genotypes AA, AG, GG were 19.4%, 51.3%, 28% and the frequencies of alleles A, G were 45.6%, 54.4%, respectively, the genotypic frequencies were in Hardy-Weinberg equilibrium (x~2=1.21, P=0.55). The distributed genotypic frequencies of AA, AG, GG were 19.7%, 52.1%, 28.2% in EH group and 19.5%, 51.9%, 28.6% in NT group, respectively. The distributed allelic frequencies of A , G were 45.8%, 54.2% in EH group and 45.5%, 54.5% in NT group, respectively. The distribution of genotypic and allelic frequencies had no significant difference between these two groups (x~2=0.01, P=0.99; x~2 =0.007, P=0.93). Through to analyze the data stratified with gender (male and female ), BMI (normoweight: BMI<24Kg/m~2; overweight: BMI≥24Kg/m~2), different age groups (≤39 years old, 40-49 years old,≥50 years old), the distribution of genotypic and allelic frequencies had no significant difference between these two groups (P>0.05). The genotypes of G3091A polymorphism were excluded as independent variables which related to the blood pressure and serum electrolytes of subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 4) Nine kinds of united genotypes were composed by T3593C and T663A polymorphisms. The distribution of the united genotypic frequencies had no significant difference between EH group and NT group (x~2 =6.449, P=0.597). There was no significant difference in level of blood pressure among subjects with the different united genotypes (P>0.05). But the serum Na~+ of the subjects with the united genotype composed by T663A AA and T3593C TT was lower than those subjects with the other united genotypes (P=0.03). And the genotypes of the united genotypes were excluded as independent variables which related to the blood pressure among subjects after controlling the confounding factors like age, gender, BMI by multiple logistic analysis. 5) The results of the first parts showed the serum K~+, Na~+ in EH group were higher but the Na~+/K~+ were lower than those in the NT group (P<0.05). 6)There were no linkage disequilibrium among G2139A, G3091A, T663A, T3593C. There were more than ten kinds of haplotypes were constituted by these four SNPs in Xinjiang Kazakhs. There were significant difference in distributed frequencies of two kinds of haplotypes between EH group and NT group. The frequency of H1 haplotype consituted by 2139G, 3091A, 663G and 3593T in EH group was significant higher than that m NT group(x~2 =7.41,P=6.482E-3), wheras the frequency of H2 haplotype composed by 2139A, 3091 A, 663A and 3593C in EH group was significant lower than that in NT group(x~2=5.23, P=0.022). Conclusions: 1) The levels of the serum K~+, Na~+ in EH group were higher but the levels of Na~+/K~+ were lower than those in NT group. 2) There existed T3593C, T663A, G2139A, G3091A polymorphisms of aENaC gene in Xinjiang Kazakhs. There were three kinds of genotypes AA, AG, GG and two kinds of alleles A, G in T663A , G2139A, G3091A polymorphisms, respectively. There were three kinds of genotypes TT, TC, CC and two kinds of alleles T, C in T3593C polymorphism. 3) Our study indicated that T3593C, G2139A and G3091A polymorphisms might not be associated with EH and serum electrolytes of Xinjiang Kazakhs except that the AA genotype of T663A polymorphisms might be associated with the higher level of the serum Na~+of Xinjiang Kazakhs. 4) The nine united genotypes composed by T663A and G3091A polymorphisms might not be associated with EH in Xinjiang Kazakhs. But the united genotypes composed by T663A GG and T3593C TT might be associated with the lower level of the serum Na~+in Xinjiang Kazakhs. 5) There were more than ten kinds of haplotypes constituted by G2139A, G3091A, T663A and T3593C. The H1 haplotype composed by the alleles with 2139G, 3091A, 663G and 3593T might be associated with EH in Xinjiang Kazakhs, however, the H2 haplotype composed by the alleles with 2139A, 3091A, 663A and 3593C might decreased the risk of EH in Xinjiang Kazakhs. 6) The salt sensitive gene --- ENaC gene are still one of the important candidate genes related to EH in Xinjiang Kazakhs.
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