The Relationship Between Gene Polymorphism Of Reninangiotensin System And Essential Hypertension

Background: Essential hypertension is a polygenic disease influenced by both inherited and environmental factors. It often leads to serious complications involving heart, brain and kidney. And it is a major contributor to stroke and coronary heart disease. Renin-angiotensin system (RAS) plays an important role in regulation of blood pressure. As a rate-limiting enzyme in cascade reactions of RAS, renin can cleave angiotensinogen (AGT) specifically to release angiotensin I, which in turn is cleaved by angiotensin converting enzyme to angiotensin II. And angiotensin II has been known as the most potent vasoconstrictor so far. Given the crucial role of renin and angiotensin in RAS, the genes encoding these two proteins have been referred to as the critical candidate genes for essential hypertension.Objective: To investigate the relationship of renin gene and angiotensinogen gene with essential hypertension among Han population in Chongqing.Methods: A case-control research was carried out among normotensive and hypertensive subjects in Han population in Chongqing. Polymerase chain reaction (PCR) technique combined with silver staining ondenaturing DNA sequencing gel was applied to genotype the (ACAG)n short tandem repeat polymorphism (STRP) of renin gene. PCR followed by restrict enzyme digestion was used to detect the AGT M235T gene polymorphism. By comparing the genotypes and allele frequency distributions of these two genes in EH and controls, we could determine whether there are associations of these two genes with essential hypertension. Results:1. Renin gene (ACAG)n-STRP: Five alleles were discovered in Han population in Chongqing. The most frequent genotype and allele of renin gene (ACAG)n-STRP are genotype 4/4 and allele 4 respectively. The genotype frequency distribution is in Hardy-Weinberg equilibrium. The frequencies of genotype and allele showed no significant difference between two groups (x2 = 3.27, P>0.05; x2=1.21, P>0.05).2. The gene polymorphism of AGT M235T: there was significant difference in the genotype distribution and allele frequency between the hypertensive and normotensive groups. The frequencies of T allele and TT genotype were significantly higher in hypertensive patients than in normotensive controls (79% vs 66%; 65% vs 48%, respectively). Comparing with MM genotype, the odds ratios exposed to MT genotype, exposed to [TT\MM] genotype and exposed to TTgenotype were 2.43, 3.23 and 3.84 respectively. It indicated that the more T allele, the higher morbidit risk of essential hypertension. (Trend test x 2=6.58, P<0.01) The odds ratio exposed to T allele was 1.96 comparing with M allele. (P<0.01). Conclusions:1. Renin gene is likely not a major contributor to the genetic bases for essential hypertension in Han population in Chongqing.2. AGT M235T gene polymorphism is closely associated with essential hypertension in Han population in Chongqing. TT genotype may be a susceptible genotype to EH in Han population in Chongqing.