A Comparative Study Of The Influence Of TLR4 Gene 3'UTR Genetic Variation On Essential Hypertension Among Han,yi And Haini Population In Yunnan Province

Background: essential hypertension(EH)is a highly heterogeneous complex human disease which can lead to a variety of cardiovascular diseases and kidney diseases.EH is Susceptibility influenced by both genetic and environmental factors.TLR4 is crucial in immune response and inflammatory response,studies on hypertension have shown that TLR4 activator or inhibitor can promote or inhibit the pathologic process of hypertension,indicate that TLR4 can affect the occurrence and development of EH by regulating immune response and inflammatory reaction.3'UTR can regulate the downstream genes.Previously our research on autoimmune diseases shows that gene polymorphisms on the TLR4 3'UTR has a significant effect on this diseases,but there is no relevant report on hypertension.In addition,the incidence of EH among Han population,Yi population and Hani population in Yunnan province is significantly different,especially the Yi and Hani population,and their incidence of EH is lower than the national average.Therefore,this study select these special Yunnan ethnic minorities—Yi and Hani as study core subjects,on the one hand,detected the genetic differences in the TLR4 gene 3 'UTR among Han,Yi and Hani population in Yunnan,on the other hand,analysis the influence of TLR4 gene 3' UTR genetic variation on EH among these three population in Yunnan.Material and Methods: A total of 1818 individuals enrolled in the study,including 1118 healthy individuals(481 cases of Han,339 cases of Yi,298 cases of Hani),700 patients with EH(283 cases of Han,218 cases of Yi,199 cases of Hani).The genetic variation of TLR4 gene 3 'UTR section was detected by direct sequencing.The sequencing results were statistically analyzed by SPSS22.0,HaploView4.2software and SHEsis online analysis tool.Result:1.There are genetic variation differences in TLR4 3'UTR section of Han,Yi and Hani people in Yunnan.TLR4 gene 3'UTR section detected 6 major SNPs in the research samples:rs41426344,rs7869402,rs11536889,rs60972665,rs7873784,rs11536891.Other forms of genetic variation were not detected.Among the 6 SNP sites,the mutation rate of rs11536889 was the highest--Hani is 0.299,Yi is 0.270,Han is 0.240;The mutation rate of rs60972665 is the lowest--Yi is 0.009,Han is 0.006,Hani is0.003.Chi-square test suggested that the alleles and genotypes of rs41426344,rs7869402,rs11536889,rs7873784 and rs11536891 were significantly different in the three populations(P<0.05).2.The influence of genetic variation of TLR4 3 'UTR on EH among Han,Yi and Hani population in Yunnan province.The results of the unit point correlation analysis show that: in Yunnan Yi and Yani population,after adjusting for age and gender,no SNPs sites in TLR4 3 'UTR were detected related to the EH.Among the Han population in Yunnan,rs60972665,rs7873784 and rs11536891 had significant differences between the control group and the case group.It is suggested that these three sites are related to the EH of Yunnan Han.rs60972665 allele C,TT genetype;rs7873784 allele G,GG genotype;rs11536891allele T and TT genotype might be a risk factor,significantly increased the risk of EH in Han population(adjusted P<0.05).Gender stratified analysis shows: rs60972665 allele C,TC genotype significantly increased the risk of EH in Han male population(adjusted P<0.05),rs7873784,rs11536891 were no no correlation with the occurrence of EH in Han male or female population.Haplotype analysis result show that the above six SNP site in the Han,Yi,Hani population respectively build 6,8,6 kinds haplotypes,a total of 8 haplotypes,named the H1-H8.H3(GCCTGT),H5(GCGTGT)are the major haplotypes in the three populations.In Han population,the H4(GCGTCC)significantly reduce the risk of EH than any other haplotypes,and H2(GCCCGT)significantly increase the risk of EHthan any other haplotypes;In Yi population,H7(CCGTGT)significantly reduce the risk of EH than any other haplotypes,H6(GTGTGT)significantly increase the risk of EH than any other haplotypes;In Hani population,H4(GCGTCC)significantly increase the risk of EH than any other haplotypes.In general,the distribution frequency of these haplotypes in different populations is generally low.Conclusion: TLR4 gene 3'UTR section of genetic polymorphism exists significant ethnic differences(except rs60972665 loci,the remaining 5 SNPs in the three population exist significant differences),the structural differences in this gene may be a part of the genetic basis of the different occurrence of EH in these ethnic groups(Han population has a higher occurrence of EH than Yi and Hani population).In the 6 SNP sites in this section,rs60972665,rs7873784 and rs11536891 are the sites that are particularly important for the relevant research of the Han population in Yunnan and essential hypertension.