Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis.

Genes involved in regulation of the nuclear factor-κB (NF-κB)-pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of , , and genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-α therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for (rs111200466), (rs4986790, rs4986791), (rs5743836, rs187084) and (rs28362491) alleles. The presence of the -1486 variant ( < 0.0001) and its homozygosity ( < 0.0001) were found to be associated with disease susceptibility. The -1237 allele was associated with predisposition to RA in females only ( = 0.005). Moreover, the rs4986791 (rs4986790 ) alleles were more frequently detected among patients with the stage IV disease ( = 0.045), and were associated with more effective response to anti-TNF-α therapy ( = 0.012). More efficient response to anti-TNF-α treatment was also observed in patients with within the gene ( = 0.047), while for the -1486 homozygotes, the treatment was ineffective ( = 0.018). polymorphisms affect disease susceptibility and response to therapy with TNF-α inhibitors in RA patients of Caucasian origin.