The Effect Of Gene Polymorphisms In Tnterleukin-4and Interieukin-6on The Susceptibility Of Rheumatoid Arthritis

Background：Rheumatoid arthritis (RA) is a complex, chronic inflammatory disease thatpredominantly involves synovial joints, leading to cartilage and bone destructionand remarkable limited range of motion in end stage. The joint function can beimproved with total joint arthroplasty to some extent but the medical cost is quitehigh. Moreover, the function improvement of RA patient is inferior to that ofosteoarthritis patients because of the increased complication rate such as infectionetc.. The diagnosis, treatment, and prevention of rheumatoid arthritis are always acentral issue. Interleukin-4(IL-4) and interleukin-6(IL-6) have been reported toassociate with pathogenesis of rheumatoid arthritis (RA); however, the role ofIL-4and IL-6genetic polymorphisms in RA remains unknown and needs furtherstudies.Objective：To investigate the effects of promoter polymorphism in IL-4-590andIL-6-174on the Susceptibility of Rheumatoid Arthritis in Chinese PopulationMethod：According to the American Criteria of Rheumatology, a total of752unrelatedChinese patients with RA and798healthy Chinese volunteers with no familyhistories of any autoimmune diseases were recruited. Both RA and control groups were interviewed to obtain demographic data and all of the established risk factors.Genomic DNA was extracted from peripheral venous blood by using the AxygenDNA isolation kit and stored at80°C. SNPs of IL-4and IL-6promoters weregenotyped by Polymerase Chain Reaction-Restriction Fragment LengthPolymorphism (PCR-RFLP).Allele and genotype frequencies of IL-4-590and IL-6-174were comparedby2analysis. The chi-squared (2test was utilized to evaluate theHardy-Weinberg equilibrium in genotypic distributions and clinical characteristicsbetween cases and controls. A level of <0.05was considered statisticallysignificant.Result：There were no significant differences in the demographic and clinicalcharacteristics of all subjects in the study and the single-nucleotide polymorphism(SNP) was found to be in Hardy-Weinberg equilibrium.As for the IL-4-590C/T, the frequency of the TT genotype was significantlyhigher among RA patients (7.05%) compared to controls (2.01%), and thefrequency of the CT genotype was also higher among RA patients (29.00%versus25.94%), but the frequency of the CC genotype was significantly lower amongRA patients (63.96%) than controls (72.06%). Accordingly, the T allele frequencywas significantly higher in RA patients than controls (21.54%versus14.97%,＜0.001).As for the IL-6-174G/C, the frequencies of the GG, GC, and CC genotypeswere81.52%,16.49%, and2.00%in RA patients, significantly different fromthose observed in controls, which were determined to be98.50%,1.25%, and0.25%, respectively (<0.001). Accordingly, the allelic frequencies in the patientsand controls were also significantly different for G allele (89.76%VS99.12%)and C allele (10.24%VS0.88%)(<0.001). Conclusion：The IL-4-590and IL-6-174promoter polymorphisms may be associated withincreased risk of RA, and could be used as genetic marker for assessing thesusceptibility of RA in Chinese. The frequencies of both the T allele on theIL-4-590and the C on the IL-6-174were significantly increased in RA patients.