Association Of Salt-sensitive Related Gene Polymorphism With Essential Hypertension In Xinjiang Kazakh Population

Essential hypertension (EH) is thought to be a complex disorders which is influenced by multiple genetic and environmental factors. Increased dietary salt is one of important environmental factors, but it is influenced by ethnic and genetic factors. Many genes polymorphisms have been proposed as possible markers for hypertension. Aldosterone synthase (CYP11B) which regulates sodium and water balance catalyzes the final step in the aldosterone biosynthesis and could therefore influence blood pressure (BP). The CYP11B2 locus (chromosome 8q22) is present in tandem with the locus for CYP11B1, which is involved in cortisol synthesis, but can influence aldosterone. CYP11B2 is a gene to be tested for association with EH, especially salt sensitive hypertension. Endothelial nitric oxide synthase (eNOS), via generation of nitric oxide (NO), is the major endothelial-derived arteriolar vasodilator. In EH, NO is reduced. NO correlates negatively with blood pressure. The eNOS is an important enzyme producing NO and maintaining the vascular dilation. Deletion of the eNOS gene leads to EH. Recently two polymorphisms, the 27-bp variable number of tandem repeat (VNTR) polymorphism in intron 4 and the Glu298Asp (G894T) substitution in exon 7 of the eNOS gene have been reported to be related to EH, especially .27-bp VNTR 4a allele may be a risk factor of hypertension.The incident rate of hypertension in Kazakh is one of the five highest nationalities in China. Barlikun country situates at the south of the Tian-shan Mountain, with high elevation and cold climate, where Kazakhherdsmen have been dwelt for a long time. Geographic environment of Balikun is blocking, and the residence there seldom married with other population outside .The diet habits of Balikun Kazakh are high saturated fats, high salt intake, and low vegetables consumptions. The genetic homogeneity and geography stability of the population, along with shared exposure to common environmental variables, provide an excellent opportunity for the study of genetic influence on hypertension.The aim of the present study is to investigate the association of the CYP11B2T-344C and eNOS polymorphism with blood pressure to evaluate the interaction of these polymorphisms with known environmental determinant (age, body mass , salt intake and et al) of these phenotypic variables in Kazakh population.Part IAssociation of the T(-344)C Polymorphism of Aldosterone Synthase Gene CYP11B2 with Essential Hypertension in Xinjiang Kazakh PopulationObjective:To investigate the association of the T( - 344)C polymorphism of aldosterone synthase gene CYP11B2 with essential hypertension in Xinjiang Kazakh population. Methods: The study covered 186 hypertensive and 168 normotensive subjects in Xinjiang Kazakh population. Age of all the subjects were ≥ 30, and /or ≤60. Biochemistry tests including blood glucose, triglyceride and cholesterol were performed in all the subjects. Hypertensives were diagnosed according to the criteria of 1978.Genomic DNA was extracted from wholeblood by the standard procedures. The segment of CYP11B2 was amplified from DNA by polymerase chain reaction (PCR). The PCR products were digested by restriction endonuclease. Results : The frequencies of C and T in hypertensive group(0.45 and 0.55)were no significant difference from the controls(0.43 and 0.57, x 2=0.380 P=0.537) .The frequencies of CC, CT, TT genotypes of CYP11B2 gene were 0.20, 0.50, 0.30 in hypertensive respectively and 0.12, 0.61, 0.27 in control group respectively .There were no significant differences in genotypes between hypertensive group and normotensive group( x 2=4.838,P=0.089).But the frequency of CC genotype in female hypertensive was higher than that in normotensive control ( x 2=6.104, P < 0.05).Glucose levels of CT and CC genotypes were higher than TT one in female hypertensive group.Conclusions: Our results suggested that the T(-344)C polymorphism of CYP11B2 gene might be associated with hypertension in female Kazakh population of Xinjiang Barlikun area, as well as it might be associated wi...