Objective: The goal of this study was to investigate whether the tumor necrosis factor– α (TNF– α) –308 G/A and –238 G/A promoter polymorphisms are associated with the risk of developing Rheumatoid arthritis (RA).

Methods: The authors conducted a comparative meta–analysis, incorporating 3131 RA patients and 3490 healthy controls from a total of 18 studies consisting of 29 separate comparisons. The tests were performed by the using fixed or random effects models.

Results: A positive association was found between TNFα–308G/A polymorphism (OR =0.845, 95%CI =0.752–0.949, P = 0.005) and TNFα –238 G/A polymorphism and RA risk by meta–analysis (OR = 0.744, 95% CI = 0.602– 0.920, P = 0.006) in the overall population. On stratification by ethnicity a significant association was found between TNFα–308G/A polymorphism and RA risk in Latin American (OR=1.578, 95%CI=1.073 – 2.320, P=0.020) and Asian (OR=0.644, 95%CI=0.501–0.828,P= 0.001) and for TNFα –238 G/A in Europeans (OR=0.595, 95%CI=0.435–0.815, P=0.001) and Latin Americans (OR=0.493, 95%CI=0.245–0.992, P=0.047).

Conclusion: Meta–analysis of available data revealed that the TNFα–308G/A polymorphisms is a susceptibility factor for developing RA in Latin Americans and Asians but not in Europeans and TNFα–238 polymorphism is susceptibility factor for RA in Latin Americans and Europeans but not in Asian population.