Molecular Epidemiology Study Of NOS3 Gene,miR-511 Gene,miR-520a(3P) Gene Polymorphism And Essential Hypertension

Objective: To provide theoretical basis for exploring the molecular mechanism of essential hypertension(EH),this study would investigate the genetic effect of NOS3 gene on the susceptibility of EH and screen the correlation mi RNAs with EH,meanwhile test the association between the polymorphisms of the encoding genes of these mi RNAs and EH in the Han Chinese population.Methods: A case-control study consists of 2012 EH patients and 2210 controls was used to evaluate the association of three clinically relevant polymorphisms(rs4496877;rs1808593;rs3918186)in NOS3 gene with EH in Chinese Han population.TDLA experimental method was used to screen the mi RNA of differential expression in peripheral blood plasma between 24 EH patients and 24 controls,and real time quantitative fluorescence PCR(RT-PCR)was conduced to further verify the differential expression of mi RNA.The association between the polymorphisms of the encoding genes of mi RNAs and EH were tested in a case-control study consists of 4222 subjects by Taq Man genotyping technology in a Chinese Han population.Stratification and haplotypes analysis were applied to further evaluate relationships between the NOS3 gene and EH,and general linear model was performed to compare blood pressure levels between genotypes.Results: Association analysis showed that there was no significant association between rs4496877,rs1808593 and rs3918186 of NOS3 and EH in the whole study population.Stratification analysis indicated that rs3918186 was significantly associated with EH in the ?55-year-old population(OR=1.245,95% CI=1.010-1.534,P=0.04).The rs4496877 and rs1808593 were significantly associated with EH in the male population(P=0.015)and <55-year-old population(P=0.025),respectively(OR=3.254,95% CI=1.257-8.425 and OR=1.683,95% CI=1.066-2.657,respectively).Quantitative trait analysis showed that there were significant differences in systolic blood pressure(SBP)among the genotypes(AA,AT and TT)of rs3918186 in the nonintervention populations(P=0.016).GMDR analysis showed that drinking and rs3918186 had significant interaction effects for risk of EH.The mi R-511 ?mi R-520a(3p)and mi R-1274 a were found different expression in EH patients and controls.Association analysis showed that there was no significant association between rs1013288(G>A)and rs11881257(G>A)and rs1926736(G>A)of and EH in the whole study population.The rs4748424(A>G)was significantly associated with EH in additive model and dominant model(P<0.01).Stratification analysis indicated that rs10413288 was significantly associated with EH in additive model(OR=1.153,95% CI=1.032-1.289,P=0.012)and dominant model(OR=1.200,95% CI=1.026-1.403,P=0.022)in the ?55-year-old population.The rs11881257 was also significantly associated with EH in additive model(OR=0.880,95% CI=0.784-0.986,P=0.028)and dominant model(OR=0.833,95% CI=0.716-0.970,P=0.019)in the ?55-year-old population.The rs1926736 were significantly associated with EH in the male population(OR=1.165,95%CI=1.015-1.338,P=0.03).The rs4748424 was significantly associated with EH in additive model,dominant model and recessive model in ?55-year-old population,the male population,the non-smoking population and the non-drinking population respectively.Quantitative trait analysis showed that there were significant differences in SBP among the genotypes(GG,GA and AA)of rs1926736 and the genotypes(AA,AG and GG)of rs4748424 in the intervention populations(P was 0.025 and 0.009 respectively)after adjusting confounding factor.Conclusions: The findings of this study indicated that the rs4496877,rs1808593 and rs3918186 polymorphisms of NOS3 contribute to the genetic susceptibility of EH and that rs3918186 was associated with SBP in the Chinese population.Age and gender might modify the genetic effect of NOS3 on EH,and drinking significantly interacts with rs3918186.The mi R-511,mi R-520a(3P)and mi R-1274 a were abnormal expression in EH and the allele G of rs4748424 might a protective factor for EH.The rs10413288 and rs11881257 polymorphisms of mi R-511 gene and rs1926736 polymorphisms of mi R-520a(3p)gene contribute to the genetic susceptibility of EH and that rs1926736 and rs4748424 was associated with SBP in the Chinese population.Age,gender,smoking and drinking might modify the genetic effect of mi R-511 gene and mi R-520a(3p)gene on EH.