OBJECTIVE: To define the frequency of the exon 6 tumor necrosis factor-alpha (TNF-alpha) receptor II (TNFRII) gene polymorphism in severe and mild-moderate rheumatoid arthritis (RA) and its possible influence on anti-TNF-alpha treatment responsiveness. METHODS: Two cohorts of patients with RA, the first (n = 97) defined as methotrexate responders (MTX-R) with mild-moderate synovitis, and the second (n = 78) defined as nonresponders to combination therapy and receiving anti-TNF-alpha treatment because of their severe and aggressive disease (TNF-T), were studied retrospectively and compared to age, sex, and ethnically matched controls (n = 84). In the prospective study, 66 patients with severe RA were followed over the first 6 months of anti-TNF-alpha therapy and their response was examined according to genotype. RESULTS: We observed a trend towards an increased frequency of the GG genotype in patients with severe RA (6.4%) in comparison with patients with mild-moderate disease (3.1%) and controls (1.2%). When looking at the response to anti-TNF-alpha therapy, we observed that after 12 weeks of treatment, 37.8% of the TT versus 10.7% of the TG/GG patients passed from high to medium-low disease activity (p = 0.03). CONCLUSION: In our cohorts of patients selected by response to the conventional therapy and by disease severity, our preliminary study results showed a trend towards a higher prevalence of the GG genotype for the exon 6 TNFRII polymorphism in the less responsive patients with more aggressive disease. We also found a lower degree of response to anti-TNF-alpha treatments in patients carrying the G allele.
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