The Association Studies Between Two SNPs Of SCNN1A Gene With Hypertension Among Kazakh And Uigur

Background:With high elevation and cold climate, Kazakh and Uigur herdsmen of Xin Jing have been dwelt in Xin Jiang for a long time. Geographic environment there is blocking, and the residence seldom marry with people outside.The SCNNIA gene, which is located on human chromosome 12pl3.3, encodes the [alpha] subunit of the amiloride-sensitive epithelial sodium channel, and mutations in SCNNIA can result in pseudohypoaldos-teronism type I. It was postulated that genetic variations in SCNNIA could lead to an increased risk of hypertension. Sequence variations in SCNNIA were identified, and the association between these polymorphisms and BP was examined in a large cohort (n=3898) representing the general population in Japan. Four polymorphisms in the promoter region, three polymorphisms in the exonic region, and one polymorphism in the first intron were identified. Because association studies with one-half of the study population indicated that the A(2139) G polymorphism, among others, significantly affected BP, this polymorphism was studied in the entire study population. A transient transfection assay using MDCK cells indicated that the promoter activity of the G(2139) allele was higher than that of the A(2139) allele. Therefore, possession of the SCNNIA G(2139) allele significantly increased the risk of hypertension. A lower level of SCNN1A subunit expression among subjects with the AA genotype might lead to lower levels of sodium reabsorption in the kidney and mightprovide protection against the development of hypertension. Objective:To investigate whether the polymorphisms in the G(2139)A and G(3091)A are associated with hypertension among Kazakh and Uigur . Method:A large number of case-control study was selected from Kazakh and Uigur. A previous medical history of diabetes and hypertension, body mass index (BMI) was recorded. Plasma glucose, triglyceride, and cholesterol were measured. The G-?A polymorphism of the above mentioned two sites were determined by the Taqman technique, and PCR-RFLP . Results:The distributions of genotypes and alleles for the two polymorphisms did not differ significantly between the case and control populations, and odds ratio of Essential Hypertension related to the two SNP was not significantly different. Further analysis showed no association between genotypes and BMI, Glu, triglyceride, cholesterol, SBP and DBP. In conclusion, the polymorphisms in the G(2139)A and G(3091)A of SCNN1A gene, solely or combined, did not confer a significantly increased risk for the development of Essential Hypertension in the Kazakh and Uigur of Xin Jing.