RORC2 Genetic Variants and Serum Levels in Patients with Rheumatoid Arthritis

Agnieszka Paradowska-Gorycka, Barbara Stypinska, Andrzej Pawlik, Katarzyna Romanowska-Prochnicka, Ewa Haladyj, Malgorzata Manczak, Marzena Olesinska, Agnieszka Paradowska-Gorycka, Barbara Stypinska, Andrzej Pawlik, Katarzyna Romanowska-Prochnicka, Ewa Haladyj, Malgorzata Manczak, Marzena Olesinska

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.

Keywords: RORc; Th17 cells; pathogenesis; polymorphisms; rheumatoid arthritis.

Figures

Figure 1
Figure 1
Sequencing map of genotype for RORc2 gene. (A) rs9826 A/G, the arrow of 1–3 showed AA, AG and GG genotypes, respectively.; (B) rs12045886 T/C, the arrow of 1–3 showed TT, TC and TT genotypes, respectively; (C) rs9017 G/A, the arrow of 1–3 showed GG, GA and AA genotypes, respectively.
Figure 2
Figure 2
Linkage disequilibrium (LD) plots of three SNPs in the RORc2 gene. The plot illustrates pairwise LD between all polymorphisms based on D′ values. Values approaching zero indicate absence of LD, and those approaching 100 indicate complete LD. The square colored red represent varying degrees of LD < 1 and LOD (logarithm of odds) > 2 scores (strong LD) and white blocks represent varying degrees of LD < 1 and LOD < 2 scores (weak LD).
Figure 3
Figure 3
RORc2 protein level in RA patients and healthy subjects.
Figure 4
Figure 4
Variation in RORc expression levels in (A) RA patients and (B) control group in relation to RORc2 genotypes: (A) rs9826 A/G, p = 0.589; rs12045886 T/C, p = 0.207; and rs9017 G/A, p = 0.776; and (B) rs9826 A/G, p = 0.106; rs12045886 T/C, p = 0.483; and rs9017 G/A, p = 0.073. p, Kruskal–Wallis test; p < 0.05 was considered significant.
Figure 4
Figure 4
Variation in RORc expression levels in (A) RA patients and (B) control group in relation to RORc2 genotypes: (A) rs9826 A/G, p = 0.589; rs12045886 T/C, p = 0.207; and rs9017 G/A, p = 0.776; and (B) rs9826 A/G, p = 0.106; rs12045886 T/C, p = 0.483; and rs9017 G/A, p = 0.073. p, Kruskal–Wallis test; p < 0.05 was considered significant.

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Source: PubMed

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