Correlation Of Renin-Angiotensin System Gene Polymorphism With Essential Hypertension And Plasma Nitric Oxide And Endothelin

Essential hypertension (EH) is a very familiar disease in cardiovascular. What is the mechanism has not been clear. EH is regarded as a multifactor and polygenic disorder, and several genes are thought to play an important role in its pathogenesis. The renin-angiotensin system (RAS) is one of the important factors that regulates the blood pressure, as well as fluid and electrolyte balance. So some correlative genes of RAS have been wildly studied. The angiogenesis II type 1 receptor (AT1R) gene and angiotensinogen (AGT) gene were regarded as logical candidate who implicated in EH. Some researches of ATIR or AGT have been done broadly. But different conclusions were drawn from different regions or ethnic groups.In the process of investigating the pathogenesis of EH, endothelial dysfunction is also regarded as implicating in initiation of EH. Endothelial lining of arterial wall is now recognized playing an important role in maintenance of normal vascular function and pathogenesis of many cardiovascular diseases including hypertension. Endothelial cells regulate relaxation and contraction or proliferation of vascular smooth muscle, platelet aggregation, coagulation and monocyte adhesion. Many researches have been found that there is endothelial dysfunction in hypertension. But weather there is heredity participates in the pathogenesis of hypertension, endothelial dysfunction is a cause or a result of hypertension has been not very clear. Objective:Our experiment was designed to investigate whether AT1R gene A1166C and AGT gene T174M, M235T polymorphism are implicated in human EH. Plasma Nitric Oxide (NO) and Endothelin (ET) were measured At the same time. Through experiment we expect to explore the relationship of RAS gene polymorphism with Plasma NO and ET, furthermore we can discuss the pathogenesis of hypertension and the cause or effect of endothelial. This will help to prevent EH and its complications earlier. Methods:We observed 100 subjects from the hypertension outpatient clinicas hypertension group and 40 normotensive subjects as control group. Hypertension was defined as systolic blood pressure (SBP) 140 mmHg or diastolic blood pressure (DBF) 90 mmHg. Secondary forms of hypertension were excluded by clinical and laboratory examination. There were no statistically significant between two groups in age and sex. All these subjects were extracted genomic DNA by Blood Cell Genomic DNA Mini-prep Kit. Polymerase chain reaction (PCR) and PCR combined with restriction enzyme digestion were used to identify the angiogenesis II type 1 receptor A1166C, AGT gene T174M and M235T polymorphism. Plasma NO and ET activities were measured by deoxidized nitric acid and Radioimmunoassay Kit. Results:1. The frequency of TM and MM genotype of T174M polymorphism was significantly higher in essential hypertension group than in control group (P < 0.05), the frequency of 235TT genotype of AGT was significantly higher in essential hypertension group than in control group (P < 0.05), furthermore, we found that the frequency of AGT 174M allele and AT1R 1166C allele was significantly higher in essential hypertension group than in control group (P < 0.05). 2. There was significant difference of the marks of endothelium relaxation and contraction dysfunction in essential hypertension group than in control group: there was lower activity of plasma NO inessential hypertension group while higher activity of plasma ET in essential hypertension group (p < 0.01).3. In EH group we found ㏕he plasma NO level of 1166CC genotype was significantly lower than that of 1166AC (P < 0.01) and 1166AA genotype (P < 0.05); The plasma ET level of 1166CC genotype was significantly higher than that of 1166AC (P < 0.05) and 1166AA genotype (P < 0.01); while there was no statistical difference of plasma NO or ET level between EH group and control group(2) The plasma NO level of 174MM genotype was significantly lower than that of 174TM and 174TT genotype (all P < 0.01); The plasma ET level of 174MM genotype was significantly higher than that of 174T...