Association Between CD14, IL-6Gene Polymorphisms And Rheumatoid Arthritis In Han Population Of Shandong Province

BackgroundRheumatoid arthritis (RA) is a complex inflammatory joint disease, characterized by erosive symmetrical polyarthritis and systemic features involving other organs, affecting approximately0.5%to1%of the adult population worldwide. Although the etiology and pathogenesis of RA was not clearly defined, a combination of risk alleles from numerous genes contributed to RA susceptibility had been found.CD14is a lipopolysaccharide (LPS) receptor existing on monocytes and macrophages.LPS first binds to LPS-binding protein (LBP), which then interacts with the TLR4/MD2complex. Binding these complexes with CD14facilitates intracellular signalling through the toll-like receptors (TLRs), induces gene activation and proinflammatory cytokines release such as IL-6et al. IL-6is a major mediator of the acute phase response and is increased in the synovial fluid and tissue in RA patients. Data has shown that CD14and IL-6play a central role both in innate immune system and in the disease progression of chronic inflammatory diseases including RA.It had been proved that single nucleotide polymorphisms (SNPs) in the promoter region of CD14and IL-6gene increased the soluble CD14and IL-6levels in serum of RA.The CD14and IL-6gene polymorphisms could be associated with RA susceptibility.ObjectiveThe aim of the present study was to investigate whether the polymorphisms of CD14gene (rs2569190and rs2563298) and IL-6gene (rs1800795, rs1800796, rs1800797, rs1524107, rs2069840and rs1474347) were associated with RA susceptibility and disease activity in Han population from Shandong province.MethodsA total of256cases with RA and331healthy controls were genotyped by high resolution melting (HRM) method. The genotype distributions and allele frequencies were calculated, association between genotype and phenotype of RA were analyzed by SPSS13.0. Furthermore, we systematically tracked all the published studies in the field and we performed a meta-analysis for more than4eligible articles studied on the polymorphisms rs1800795and rs1800796of IL-6gene in European and Asian.ResultsSignificant difference was found in rs2569190allele frequencies between RA and controls (P=0.017), no difference was observed in genotype distributions between two groups (P=0.058). There was no difference in rs2563298genotype distributions and allele frequencies between two groups (P=0.444,0.599). Significant difference was found in rs1800795, rs1800797and rsl474347of IL-6gene in genotype distributions and allele frequencies between two groups (P<0.05).The genotype distributions and allele frequencies of IL-6gene1800796, rs1524107and rs2069840in RA patients did not differ from control subjects (P>0.05).No difference was found in age, gender, disease duration, DAS28level and other laboratory parameters among different genotypes of the8SNPs. The results of the meta-analysis showed strong correlation between rs1800795and RA in Asian (P<0.00001), but no association was found between rsl800795and RA in European (P=1.00).The IL-6polymorphisms rs1800796was not evidently associated with RA susceptibility in Asian (P=0.82).ConclusionThis study suggested that CD14gene polymorphisms rs2569190and IL-6gene polymorphisms rs1800795, rs1800797and rs1474347may play an important role in the susceptibility and pathogenesis of RA in Shandong Han population.