Abstract

Rheumatoid arthritis (RA) is a complex multifactorial disease caused by environmental influences and an unknown number of predisposing genes. The present study was undertaken in order to investigate the possible association between RA disease and the TNFgene promoter polymorphisms -308A>G, -1031 T>C and the TNFβ polymorphism+252A>G (LTA252A>G) in the Tunisian population. We compared the distribution of TNF -308; TNF -1031 and LTA252 polymorphisms of TNF gene between 108 patients with RA and 226 healthy controls using PCR-RFLP analysis. No deviation from Hardy-Weinberg equilibrium was detected in either set of cases or controls. The LTA252 G allele frequency was significantly increased in RA patients (p=0.01; χ²= 6.57 OR = 0.64, 95% CI = 0.45 to 0.91). The frequency of the LTA252GG genotype was significantly higher in RA patients than in healthy controls (p = 0.004; χ² = 8.15; OR = 1.99, 95% CI = 1.20 to 3.29). TNF-1031C allele frequency was significantly increased in patients with Remission RA activity (p = 0.0035; χ² = 8.52; OR = 6.18; 95% CI = 1.45 to 3.20). These results suggest that the LTA252A>G polymorphism of the TNF gene can be associated with the susceptibility to Rheumatoid Arthritis in our study group and the TNF-1031C allele seems to be involved in remission of RA activity. Therefore, the TNF molecule may have an important genetically and/or functionally implication in the pathogenesis of RA disease in Tunisian population.

Key words: Rheumatoid arthritis, genetic susceptibility, TNF polymorphisms, polymerase chain reaction restriction fragment length-polymorphism.