Inhibitor IκBα Promoter Functional Polymorphisms in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammation disease that may involve extra-articular organs in addition to joints. Many proinflammatory cytokines are involved in the inflammatory process of RA. I kappa B alpha conjugates with NF-kappa B and is a key player in regulation of the inflammatory process. We carried out experiments to define the effect of different promoter polymorphisms on the transcriptional activities of I kappa B alpha promoter and the development of RA. Different I kappa B alpha promoter reporters were constructed and were examined in human mononuclear cells, THP-1 cells. One hundred forty patients and 115 healthy controls were recruited from the Kaohsiung Medical University Hospital. The activities of I kappa B alpha promoter constructs with -826C, -550A, -519T, and -826T, -550A, -519T genotypes were expressed at one half the activity level of other constructs. Promoter constructs containing the sites -550A/T and -519T had a reduced risk of rheumatoid arthritis. The odds ratio of -826C/T genotype was significantly associated with an increase of risk in causing rheumatoid arthritis, whereas -826T/T genotype was associated only with a slightly increased risk of RA, but without statistical significance (odds ratio = 1.2; 95% confidence interval, 0.4-3.8). The increase of T allele was associated with a significant increased risk and the tendency to the pathogenesis of RA. The association between I kappa B alpha promoter polymorphisms and disease severity of rheumatoid arthritis is partly due to different transcriptional activities of I kappa B alpha promoter and the activation of NF-kappa B.