PSORS1C1 may be involved in rheumatoid arthritis

Abstract

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.