Association Of Endothelial Nitric Oxide Synthase Gene Polymorphism With Essential Hypertension

Objective:Nitric oxide (NO) is a endothelium-derived relaxing factor, it can controll vascular tension and regulate blood pressure. It is produced by oxidation of L-arginine to L-citruline for the action at the endothelial nitric oxide synthase (eNOS) and is considered as a protection factor of vascular. In recent years, it is found that the polymorphism of eNOS gene is related with essential hypertension (EH). We investigate the relationship between exon7th894site, intron12th rs1800780site, intron14th rs3918181site and intron4th the variable number of tandem repeats (VNTR) of27bp polymorphisms of eNOS gene and EH in Han people living in Tianjin.Methods:Three hundred and eight patients with EH and one hundred and eighty one healthy people were collected in Tianjin chest hospital from June2011to November2012. All patients with EH we collected were according to the WHO/ISH criteria of hypertension diagnosis. We collected the clinic data including weight, height, smoking history, drinking history and so on. The level of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fibrinogen (FIB) were determined in all subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or polymerase chain reaction (PCR) method was used to detect genetypes of894site, rs1800780site, rs3918181site and27bp VNTR in all subjects. The relationship between genotypes and pathogenesis of EH was analyzed. The SPSS19was used in all statistical. The t test was used to compare the mean between two groups. The Pearson x2statistics were calculated between genotype distribution and allele distribution. Logistic regression analysis was used to analyze the risk of EH. Statistical significance was defined as P<0.05.Results:Age, BMI, TC and LDL-C were higher in EH group than in control group, and the differences were significant (P<0.05). The distributions of genotype in EH group and control group were in agreement with the frequencies predicted by the Hardy-Weinberg equilibrium (P>0.05). There were no significant differences in frequencies of genotype and allele distribution in894site between two Groups (P> 0.05). The frequencies of AA, AG, GG genotype in rs1800780cite in EH group were16.9%,60.7%,22.4%, while in control group were27.1%,58%,14.9%, The frequencies of A, G allele in EH group and control group were47.2%,52.8%;56.1%,43.9%respectively, There were significant differences in frequencies of genotype and allele distribution between two groups (P<0.05). We use Logistic regression analysis with presence of EH as the dependent variable (no:0, yes:l), rs1800780site gene polymorphism (AA:0, AG/GG:1) as independent variables, finding G allele of rs1800780site was a independent factor of EH(OR=1.828,95%CI:1.173～2.847, P=0.008). The frequencies of AA, AG, GG genotype in rs3918181cite in EH group and control group were28.2%,38.3%,33.4%;18.8%,43.1%,38.1%respectively, There was significant difference in frequencies of genotype distribution between two groups (P<0.05). The frequencies of A, G allele in EH group and control group were47.9%,52.1%;40.3%,59.7%respectively, There was significant difference in frequencies of allele distribution between two groups (P<0.05). We use Logistic regression analysis with presence of EH as the dependent variable (no:0,yes:l), rs3918181site gene polymorphism (G:0, AA/AG:1) as independent variables, finding A allele of rs3918181site was not the independent factor of EH(OR=1.244,95%CI:0.849-1.824, P=0.263). There were no significant differences in frequencies of genotype and allele distribution of27bp VNTR between two groups (P>0.05). The independent risk factors of EH were G allele of rs1800780site, age, BMI.Conclusions:The polymorphism of eNOS894site was not associated with EH. The polymorphism of rs1800780site was associated with EH, and the G allele of rs1800780site was a independent risk factor of EH. The polymorphism of rs3918181site was associated with EH, but it was not a independent risk factor of EH. The polymorphism of27bp VNTR was not associated with EH. The other independent risk factors of EH were age and BMI.