Abstract
Background: In the present study, we aimed to evaluate whether polymorphisms within the RORc2 gene are involved in the risk and severity of rheumatoid arthritis (RA). Methods: 591 RA patients and 341 healthy individuals were examined for RORc2 gene polymorphisms. Serum retinoic acid receptor-related orphan receptor C (RORc) levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: The rs9826 A/G, rs12045886 T/C and rs9017 G/A RORc2 gene SNPs show no significant differences in the proportion of cases and control. Overall, rs9826 and rs9017 were in high linkage disequilibrium (LD) with D’ = 0.952 and r2 = 0.874, except rs9826 and rs12045886; and rs12045886 and rs9017 in weak LD. The genotype–phenotype analysis showed a significant association between RORc2 rs9826 A/G and rs9017 G/A single nucleotide polymorphisms (SNPs) and median of C-reactive protein (CRP). Serum RORc levels was higher in RA patients with rs9826AA, rs12045886TT and -TC, and rs9017AA genotypes compared to healthy subjects with the same genotypes (p = 0.02, p = 0.04 and p = 0.01, respectively). Moreover, the median of RORc protein level was higher in RA patients with number of swollen joints bigger then 3 (p = 0.04) and with Health Assessment Questionnaires (HAQ) score bigger then 1.5 (0.049). Conclusions: Current findings indicated that the RORc2 genetic polymorphism and the RORc2 protein level may be associated with severity of RA in the Polish population.
Highlights
Since increasing interleukin (IL)-17 concentrations were observed in autoimmune diseases, increased attention has led to a precise definition of the role of human Th17 cells and their products in the process of ongoing immune response involved tissues [1,2,3]
The RORc2 rs9826 A/G, rs12045886 T/C and rs9017 G/A polymorphism genotype distribution were in Hardy-Weinberg equilibrium (HWE) in both patients and control group (Table 1)
We found no association between examined RORc2 and susceptibility to rheumatoid arthritis (RA), we analyzed the potential association between both the RORc2 gene single nucleotide polymorphisms (SNPs) and laboratory and disease activity parameters in our RA group
Summary
Since increasing interleukin (IL)-17 concentrations were observed in autoimmune diseases, increased attention has led to a precise definition of the role of human Th17 cells and their products in the process of ongoing immune response involved tissues [1,2,3]. The role of Th17 cells and Th17-associated cytokines in the pathogenesis of rheumatoid arthritis (RA) is widely recognized. Th17 cell produce several cytokines including IL-17, IL-17F, IL-6, IL-21, IL-22 and tumor necrosis factor-alpha (TNF-α) that play a key role in the RA and in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA), and they induces dendritic cells (DCs) to produce IL-12 and interferon (IFN-c) [5,6,7,8,9,10]. Knockdown of transcription factor RORc cause high Foxp levels and reduces expression of pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, IFN-γ and TNF-α, suggesting that the role of RORc2 in Th17 cells differentiation involves in induction of Th17 characteristics genes, and suppression of Treg cells specific programs [18,19,20]. Conclusions: Current findings indicated that the RORc2 genetic polymorphism and the RORc2 protein level may be associated with severity of RA in the Polish population
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