PSORS1C1 may be involved in rheumatoid arthritis

•SNPs in PSORS1C1/CDSN have a strong association with RA. The result was confirmed with two genotyping methods, Taqman and Sequenom MassARRAY.•PSORS1C1 had significantly increased expression in the blood and synovial tissues from RA patients.•The PSORS1C1 expression suppressed IL-1β and IL-17 production in the cultured RA synovial fibroblast cells following the anti-PSORS1C1 siRNA treatment.•The PSORS1C1 expression suppressed cell proliferation of the cultured RA synovial fibroblast cells following the anti-PSORS1C1 siRNA treatment.

PSORS1C1/CDSN is a susceptibility gene for psoriasis. Both psoriasis and rheumatoid arthritis (RA) are autoimmune diseases. This study investigated whether PSORS1C1/CDSN was involved in RA. The TagSNPs rs3130983, rs3778638 and rs4959053 in the PSORS1C1/CDSN locus were shown to predict susceptibility to RA in two independent RA cohorts using a TaqMan genotyping assay and Sequenom MassARRAY. The expression of PSORS1C1/CDSN was determined with western blotting and ELISA. Cultured synovial fibroblasts from RA patients (RASF) were treated with anti-PSORS1C1 siRNA. The TaqMan genotyping assay demonstrated significant differences in the rs3130983 and rs4959053 allele frequencies (p = 0.002001 and 1.74E−07, respectively) and genotype frequencies (0.010503 and 1.07E−06, respectively) between the RA patients and controls. Sequenom MassARRAY results indicated that SNP rs3778638 allele frequency and genotype frequency were significantly associated with RA (p = 7.35E−05 and 0.000357, respectively). Western blotting revealed a significant increase in expression of PSORS1C1 in RA synovial tissues, and ELISA detected high levels of PSORS1C1 and CDSN in the blood of RA patients. PSORS1C1-siRNA treatment significantly decreased the PSORS1C1 expression, IL-17 level, Il-1β level and cell proliferation in RASF. These results suggest that PSORS1C1 might play an important role in the development of RA.