Association Between IL-18Gene Polymorphisms And Rheumatoid Arthritis In Han Population Of Shandong Province

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune disease,characterized by erosive joint synovitis which can eventually lead to joint deformities and dysfunction. 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.Many studies have shown that cytokines are important mediators of the immune and inflammatory responses,they play important roles in the pathophysiology of joint inflammation and damage. IL-18belongs to IL-1family,is an important regulator of innate and adaptive immune immunity.IL-18was expressed by the monocyte/macrophage,combined with receptor in macrophage,directly induced the synthesis of TNF-α,which up-regulated intercellular adhesion molecule1(ICAM-1),production.ICAM-1could enhance the white blood cells adhesion and penetration to vascular endothelial.In vitro, TNF-a inhibit synthesis of collagen,accelerate the arthritis injury and promote the formation of pannus,etc.The serum level of IL-18was higher in RA patients than in the control groups. Data shown that the expression level of IL-18is affected by its single nucleotide polymorphisms(SNPs) in its promoter region,which implied that IL-18gene polymorphisms may be associated with RA.ObjectiveThe aim of the present study was to explore the association between the polymorphisms of IL-18(rs7106524, rs1946518, rs360718, rs5744247, rs5744280) with RA susceptibilityand disease activity in Han population from Shandong province. Methods168RA patients and242healthy controls were genotyped by high resolution melting(HRM)methods.The genotype distributions and allele frequencies were calculated,association between genotype and phenotype of RA were analyzed by SPSS13.0.Furthermore,we performed a meta-analysis based on published dataset.ResultsThere were no difference in rs710652、rs1946518、rs360718、rs5744247、 rs187238genotype distributions and allele frequencies between RA and controls(p>0.05). The genotype CC and allele C in rs5744280were associated with RA(P=0.0012、0.00123)。The results of the meta-analysis showed that the genotype CC、allele C and allele C in Asian population in rs1946518were associated with RA (OR=1.40,95%CI=1.06～1.86, p=0.03; OR=1.20,95%CI=1.02～1.41, p=0.02; OR=136,95%CI=1.05-1.76, p=0.02; respectively); Allele C in Asian population in rsl87238were also associated with RA (OR=0.78,95%CI=0.62-0.98, p=0.03). ConclusionsThe current study suggested that rs7106524、rs1946518、rs360718、rs5744247、 rs187238were not associated with RA in Shandong Han polulation. rs5744280might play a protective role in RA.IL-18gene polymorphisms rs1946518and rs187238might play an important role in the susceptibility and pathogenesis of RA.Races,genotyping methods,sample size might contribute to the conflicting results.