The aim of the study was to identify 2 polymorphic variants in the promoter region of the Foxp3 gene and their possible association with susceptibility to and severity of rheumatoid arthritis (RA). The association between genetic factors and pathogenesis suggests that T cells take part in the induction of RA. The CD4+CD25highFoxp3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis.
Patients with RA (n = 274) and healthy individuals (n = 295) were examined for -3279 C/A and -924 A/G Foxp3 gene polymorphisms by the polymerase chain reaction-restriction fragment-length polymorphism method. Serum Foxp3 levels in patients with RA and controls were measured with ELISA.
Foxp3 -3279 A and -924 G alleles were associated with significantly elevated risk of RA in the population tested (p = 0.003 and p = 0.004, respectively) compared to the wild-type alleles. Overall, -3279 C/A and -924 A/G Foxp3 gene polymorphisms were in indistinct linkage disequilibrium with D' = 0.481 and r(2) = 0.225. From 4 possible haplotypes, frequencies of 2 (AG and CA) showed significant differences between both examined groups (respectively, p < 0.001 and p = 0.007). After appropriate adjustment of Bonferroni correction for multiple testing, the genotype-phenotype analysis showed no significant correlation of the Foxp3 -3279 C/A and -924 A/G polymorphisms with the disease activity, joint damage, laboratory variables, and extraarticular manifestation in patients with RA. Serum Foxp3 level was significantly higher in patients than in controls (p < 0.0001).
Current findings indicated that the Foxp3 genetic polymorphism and the Foxp3 protein level may be associated with susceptibility to RA in the Polish population.