title: 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.
authors.affiliation: Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong University, Jingshi Road 16766, Jinan, Shandong 250014, PR China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Sun
authors.forename: Yifang
authors.initials: Y
authors.lastname: Xia
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Yuejian
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D002097:C-Reactive Protein / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D055815:Young Adult
chemical_list: C109656:CDSN protein, human; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; D053583:Interleukin-1beta; C484393:PSORS1C1 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D002097:C-Reactive Protein
keywords: CDSN; Interleukin-17 (IL-17); Interleukin-1β (IL-1β).; PSORS1C1; Rheumatoid arthritis (RA)