Association Study Of RA And Signal Transduction Of TLR Gene Polymorphism

Background:Rheumatoid arthritis is a systemic autoimmune disease, mainly manifested as chronic symmetric multi joint damage, and its etiology and pathogenesis has not been clarified. With the development of immune genetics, more and more studies have found that innate immunity plays an important role in the pathogenesis and disease progression of RA. TOLL-like receptor signaling pathway is the classical pathway mediated innate immunity. In recent years, there was much focus on the research of TOLL like receptor signal transduction pathway and autoimmune diseases. The TLR signal transduction pathway consists of myeloid differentiation factor88dependent pathway and MyD88independent pathway. MyD88dependent pathway is the most common way of TLR signal transduction pathway.MyD88and TRAF6are important adaptor proteins in this pathway. If screening on MyD88, TRAF6gene mutation sites in patients with RA, it is possible to understand the role of innate immunity in the pathogenesis of RA from the perspective of genetics.Objective:making gene sequencing on MyD88, TRAF6exon coding region in patients with RA, try to find mutations in patients with RA in the region, in order to further explore the association of RA and MyD88, TRAF6gene polymorphism in Toll like receptor signaling pathway.Methods:1. Selected whole blood samples from30patients with RA and extracted DNA.2. By polymerase chain reaction, amplified DNA fragment, identified and purified its product.3. Try to find new mutations by sequencing MyD88, TRAF6exon5coding region respectively.Results:MyD88, TRAF6gene exon5coding region sequences in30cases of RA specimens of DNA are consistent with the known sequences of the gene pool.Conclusion:New. mutations of MyD88, TRAF6gene exon coding region in patients with RA were not found. Background:Research shows that innate immunity plays an important role in the pathogenesis and progression of RA, and the relation between Toll-like receptors (TLRs) and RA progression become a hot topic in recent years. MyD88is a necessary adaptor molecule of the signaling pathway of TLR family members, mediated signal transduction in the upstream to the downstream and involved in TNF-a, IL-1, IL-6and other inflammatory factors activation, therefore, to investigate the correlation between the gene polymorphism of MyD88and its downstream inflammatory factor and RA, can contribute to understand the etiology and pathogenesis of RA.Methods:1. Select162cases of RA patients and188normal controls of whole blood samples to collect the antibody datas of RF-IgA, RF-IgG, RF-IgM, CCP, RA33, GPI.2. Extract DNA and genotype of the SNP locus of rs7744.3. Statistical analysis genotype and allele frequencies between the case group and control group.4. Statistical analysis the relationship between patients with RA genotype frequencies, allele frequencies and the clinical phenotype.Results:1. There was no statistical difference between the case group of MyD88locus of rs7744and the control group of three kinds of genotype frequencies of AA, AG, GG (P>0.05) and no significant difference in the frequency of A/G allele (P>0.05).2. The AG genotype of GPI positive RA patients was higher than that of GPI negative RA patients, which respectively57.7%,35.3%(P<0.05).Conclusion:1. There was no gender differences in patients with RA genotype frequencies of rs7744and frequency of genotype.2. There was no statistical difference in patients with RF-IgA, RF-IgG, RF-IgM, CCP, RA33positive and patients with RF-IgA, RF-IgG, RF-IgM, CCP, RA33negative.3. AG heterozygous genotype has higher proportion in GPI positive RA patients, suggesting that rs7744heterozygous genotype AG may be associated with RA antibody GPI. Background:Rheumatoid arthritis is a multifactorial disease, genetic factors and environmental factors play an important role in the progression of it. The activation of Toll like receptor (TLR)/IL-IR signaling pathway was significantly related with the occurrence and development of rheumatoid arthritis. In this signaling pathway, the activation of TRAF6can promote the expression of inflammatory factors, which leads to worsening of rheumatoid arthritis. By exploring the association of TRAF6gene mutation and RA, the study attempt to further define the correlation between them.Methods:1. Select162cases of RA patients and188normal controls of whole blood samples to collect the antibody datas of RF-IgA, RF-IgG, RF-IgM, CCP, RA33, GPI.2. Extract DNA and genotype of the SNP locus of rs030445.3. Statistical analysis genotype and allele frequencies between the case group and control group.4. Statistical analysis the relationship between patients with RA genotype frequencies, allele frequencies and the clinical phenotype.Results:1. There was no statistical difference between the case group of TRAF6locus of rs5030445and the control group of three kinds of genotype frequencies of AA, AG, GG (P>0.05) and no significant difference in the frequency of A/G allele (P>0.05).2. There were no statistical differences in gender, RF-IgG, RF-IgM, CCP, RA33, GPI and rs5030445genotype frequencies and allele frequencies in seven clinical phenotypes of RA. The A allele frequency of RF-IgA positive RA patients was higher than that of RF-IgA negative, which respectively14.6%,6.8%(P<0.05).Conclusion:The frequency of RF-IgA positive may have higher chance in patients with A allele on TRAF6rs5030445locus, and the A allele maybe the susceptibility gene of RA. Background:Rheumatoid arthritis is the result of the interaction of genetic and environmental factors. And the susceptible gene has close relationship with RA. In the pathogenesis of rheumatoid arthritis, IL-1is not only involved in the formation of synovial inflammation and pannus, but also plays an important role in bone and cartilage destruction.IL-6is a proinflammatory cytokine, capable of inducing IFN-y and tumor necrosis factor a and the expression of various chemokines, and closely related with the pathogenesis of RA. By studying the association of IL-1RAP, IL-6, IL-6R gene polymorphism and rheumatoid arthritis, from the point of view of genetics further explore the IL-1RAP, IL-6, IL-6R in the pathogenesis of RA.Objective:IL-1rap in patients with RA, IL-6, IL-6r exons code area regional gene sequencing, trying to find out RA patients with mutations in the region, in order to further explore toll-like receptor signaling pathways in the IL-1rap, IL-6, IL-6r gene polymorphisms associated with RA.Methods:1. Selected162cases of RA patients and188normal controls of whole blood samples to detect patients with RA RF-IgA, RF-IgG, RF-IgM, CCP, RA33, GPI antibodies.2. Extracted DNA, genotyping of IL-1RAP loci rs766442(IL-1RAP), IL-6loci rs6946864(IL-6), IL-6R SNP loci rs11265618(IL-6R), rs4845626(IL-6R).3. Statistical analysis genotype and allele frequencies between the case group and control group.4. Statistical analysis the relationship between patients with RA genotype frequencies, allele frequencies and the clinical phenotype.Results:1. The differences between the RA groups of IL-1RAP rs766442genotype, allele frequency and the normal control group were statistically significant (P<0.05). The RF-IgG positive RA patients with TT genotype proportion (84.8%) is higher than that of RF-IgG negative RA patients (70.3%), and the difference was statistically significant (P<0.05).2. There was no statistical difference between RA group IL-6SNP loci rs6946864genotype, allele frequencies and normal control groups.3. There was no statistical difference between group RA IL-6R SNP loci rs4845626genotype, allele frequency and normal control group. IL-6R SNP site rsl1265618genotype frequencies and normal control groups was not statistically significant. There were significant differences between C/T allele frequency of0.928/0.108in group RA and the allele frequency of0.941/0.059in the normal control group(P<0.05).Conclusion:1. The TT genotype of IL-1RAP rs766442may be the susceptible gene for RA, patients carrying the T allele of the RA may have a higher risk of positive RF-IgG rate.2. The IL-6R SNP site of rs11265618T allele is a susceptible gene for RA, but was not found to be associated with the various clinical phenotype of RA gender, RF-IgA, RF-IgG, RF-IgM, CCP, RA33, GPI.