Polymorphisms in Tnfa and Il10 Gene Promoters and Risk of Rheumatoid Arthritis in Bulgarian Population

PURPUSE: The aim of this study was to investigate the involvement of functional interleukin 10 (IL-10) and tumor necrosis factor  (TNF-) promoter polymorphisms on the susceptibility to rheumatoid arthritis (RA) in Bulgarian population. METHODS: Genotyping for -1082A/G IL10 (rs1800896) and 308G/A TNFA (rs1800629) polymorphisms were performed using allele specific PCR and restriction fragment length RLFP-PCR assays, respectively, in 135 RA patients and 179 healthy controls. RESULTS: No association between the rs1800629 polymorphisms and RA risk in Bulgarian was established. In contrast, an association between rs1800896 and susceptibility to RA was demonstrated. There was an increase of the IL10 -1082G allele (43% vs 36.3%, p=0.091) and a higher frequency of GG genotype (20% vs 12.8%; p =0.073) in cases versus controls. In logistic regression analysis the presence of high IL-10 producer genotype (-1082GG) was associated with 1.7 times higher risk of developing RA. When analyzing the influence of combined IL10/TNFA genotypes on RA appearance, we found that the carriage of both high cytokine producing genotypes of two polymorphisms (IL10 -1082GG and TNFA 308AA/GA, respectively) significantly increased the risk of developing RA with OR=4.95 (p=0.029). CONCLUSIONS: Our result showed that IL10 rs1800896, but not TNFA rs1800629 gene polymorphism is associated with genetic predisposition to RA in Bulgarian population. However, IL10/TNFA interaction further influences RA susceptibility suggesting a genetic predisposition to abnormal immune regulation in this chronic inflammatory disorder.