The Association Between Rheumatoid Arthritis And TLRs、PADI4Gene Site Polyorphism

Background With the clinical characteristic of a common.frequently-occurring and disabling disease, rheumatoid arthritis (RA) influences on human health severely.Toll-like receptors (TLRs),a important type of receptors family,could be recognized key players in innate immunity and bridges between innate and adaptive immune responses. An increasing series of circumstantial evidence implicates that TLRs play significant role in the pathogenesis of RA.The present of the study is aimed to investigate the relationship between the gene site according to the signal pathway of TLR2/4and RA,and help identify the pathogenesis of RA.Objectives To explore the association between RA and five SNPs polymorphism as follows:rs3804100for TLR2, rs4986790for TLR4, rsl152888for IRAK3, rs11926277for IRAK2and rs4251513for IRAK4gene, help identify the pathogenesis of RA and provide evidence for the prevention of RA.Methods A case control study was designed to enroll220RA patients and183healthy controls of Shandong province. We performed genotyping the following SNPs:rs3804100, rs4986790, rs1152888,rs11926277and rs4251513by using High resolution melt analysis (HRM) assays and DNA sequencing.Results rs11926277for IRAK2gene polymorphism is associated with rheumatoid arthritis in Chinese people from Shandong province (P<0.05).There were no significant differences in the frequency of the rest of SNPs genotypes and alleles between RA cases and healthy controls (P>0.05).Conclusions The result of association study could be partly effected by many aspects such as areas and ethnic variations, genotying, the interaction between genes,etc. No significantly association was found between RA and the rs3804100for TLR2, rs4986790for TLR4, rs1152888for IRAK3and rs4251513for IRAK4gene polymorphism from Shandong province. The association between RA and other SNPs according to the signal pathway of TLR2/4need further investgation. The enlarged sample size and haplotype based research would be valuable. Objectives Published data shown that peptidylarginine deiminase type Ⅳ (PADI4) gene might be associated with rheumatoid arthritis (RA), but the conclusions are not completely same. The aim of the study was to perform a comprehensive analysis on the published data to get a reliable conclusion.Methods By selecting five SNPs in PADI4(rs11203366, rsl1203367, rs874881, rs2240340,rs1748033) which had been extensively examined,31published papers, including22papers in english and9papers in chinese, were searched from China Biology Medicine disc(CBMdisc), Pubmed and Hugenet with the keywords " rheumatoid arthritis "," peptidylarginine deiminase type Ⅳ "," single nucleotide polymorphisms " in both chinese and english. Meta-analysis on each SNP were did step by step via Review Manager5.0to investigate the association of the polymorphisms of the PADI4gene with rheumatoid arthritis(RA) from two aspects, population stratification and sample size, respectively.A linkage disequilibrium study was also performed via Haploview.Results Meta-analysis enrolled15659RA patients and22019healthy controls from21studies worldwide.It demonstrated that rs11203366, rsl1203367, rs2240340and rs1748033confer susceptibility to RA in the yellow race (P<0.00001,0.03,<0.00001,<0.00001respectively), rs11203366, rs11203367and rs874881confer susceptibility to RA in Caucasian of European ancestry (P=0.0002,0.004,0.03respectively). It also shown that no significant association between rs874881and RA in the yellow race of Asia populations (P=0.2), or rs2240340, rs1748033and RA in Caucasian of European ancestry (P=0.18and0.11respectively). According to the sample size, no association was found on the condition that the RA cases≤300 between rs874881and RA (P=0.20). A linkage disequilibrium study was also performed. The LD study shown that rs11203366, rs11203367, rs874881, rs2240340and rs1748033were in linkage disequilibrium both in the yellow race and Caucasian, which was basically consistent with meta-analysis. The conflicting results should be explained by many aspects such as bias in sample selection, genotyping, stratification, etc.Conclusions The PADI4genotype were partly associated with RA, the underling mechanisms need further study, haplotype based research and meta-analysis would be valuable.