The influence of a TNF gene polymorphism on the severity of rheumatoid arthritis in the Brazilian Amazon.

Purpose: The aim of this study was to investigate the influence of the TNF -308 G/A polymorphism in the promoter region of the tumor necrosis factor-α gene on the susceptibility and severity of rheumatoid arthritis (RA) in individuals from the Brazilian Amazon.

Methods: A total of 323 individuals-192 healthy controls without arthritis and 131 individuals suffering from arthritis-were genotyped for this polymorphism using a methodology based on PCR-RFLP.

Results: The frequency of the A allele (TNF2) in rheumatoid arthritis sufferers was not significantly higher than in the controls (p=0.926; OR=0.97; confidence interval 0.54-1.76). However, using a logistic regression model, when the patients were stratified according to whether the manifestations were preponderantly articular or systemic, there was a strong association between the TNF2 allele and systemic arthritis (p=0.001; OR=5.89; confidence interval=1.98-17.5) as well as the use of anti-TNF immunotherapy (p=0.023; OR=1.10; confidence interval=1.00-1.14). The main factors that were found to influence the risk of extra-articular disease were age greater than or equal to 60 years (p=0.008; OR=4.06; confidence interval=1.45-11.38), disease duration greater than 10 years (p=0.031; OR=3.10; confidence interval=1.11-8.63) and positive rheumatoid factor (p=0.035; OR=2.07; confidence interval=1.05-4.09).

Conclusions: These results suggest that the TNF2 allele is associated with the more serious forms of the disease in individuals from the Brazilian Amazon but not with a risk for developing RA.