Study On The Correlation Of TLR4 Gene Polymorphism With The Pathogenesis Of Rheumatoid Arthritis

Objective: To investigate the correlation of TLR 4 gene polymorphism and the pathogenesis of rheumatoid arthritis(RA),we genotyped and analyzed 16 SNP sites on Toll-like receptor factor 4(TLR 4)gene in this study.Methods: 1.135 cases of RA patients and 160 cases of normal control in Quanzhou area of Fujian were collected for the research object.We used allele-specific amplification(AS-PCR)with whole blood as template to detecte the genotype of 16 SNP sites on TLR4 gene.2.Using case-control method,with the help of SPSS17.0,online analysis tool called SHEsis to analyze the data statistically by chi-square test,t-test and logistic regression analysis,including Hardy-Weinberg balance test of 16 SNP sites,correlation of genotype or allele with RA,Linkage disequilibrium(LD)analysis among sites,analysis of haplotypes and haplotype.Results: 1.Single SNP site analysis:(1)Sites located at 3’ of the gene: site rs7873784,genotype GG has a high risk of disease(P=0.011,OR=9.495,95% CI=1.169-77.131),allele G did not show an increase risk of disease in our study;Site rs7037117,genotype GG has a high risk of disease(P=0.009,OR=3.141,95% CI=1.285-7.681),allele G has a high risk of disease(A vs.G,P=0.005,OR=1.708,95%CI=1.175-2.484);(2)Sites located at 5’ of the gene: site rs10116253,genotype CC has a high risk of disease(P=0.015,OR=2.230,95% CI=1.162-4.280),allele C has a high risk of disease(T vs.C,P=0.030,OR=1.439,95%CI=1.036-2.000);Site rs10759930,genotype CC has a high risk of disease(P=0.035,OR=2.142,95% CI=1.050-4.371),allele C has a high risk of disease(T vs.C,P=0.027,OR=1.446,95%CI=1.042-2.008);2.Multiple SNP sites analysis: The LD analysis was performed on RA patients and normal controls.Combined with sites that associated with RA,in the analysis of D’ value,rs7873784 and rs10759930 were lower in RA group(0.68 and 0.92 respectively in RA group and normal group),in r2 value analysis,rs10116253 and rs10759930 were lower in RA group(0.59 and 0.90 respectively in RA group and normal group);In haplotype analysis,haplotype AAGGCATTACGACGGC*(P=0.042,OR=0.530,95%CI=0.285-0.984)and AGGGCATTACGACGGC*(P=0.036,OR=1.897,95%CI=1.035-3.478)have a statistically difference between the RA case group and the normal control group.Conclusion: 1.After correction,4 site of 16 SNP sites selected in this study,related to the pathogenesis of RA.According to the location of the sites,suggesting that different location leads to different functions of the SNP,show differences in the pathogenesis of RA;2.In this study,16 SNP sites were analyzed jointly.We obtained differences in the LD between the two groups,identified the site most closely related to the pathogenesis of RA,suggesting that the method to analyze sites jointly is more systematic and practical.