Polymorphisms in STAT4, IL10, PSORS1C1, PTPN2 and MIR146A genes are differently associated with prognostic factors in Italian patients affected by Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is a systemic autoimmune disease resulting in chronic inflammation of the synovium and consequent cartilage and bone erosion. RA is strongly associated with the presence of rheumatoid factor (RF) and consists of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and negative patients. This study was designed to evaluate whether relevant single nucleotide polymorphisms (SNPs) associated with RA and other autoimmune disorders are related to RF, ACPA, and clinical phenotype in a cohort of biologic-naive Italian RA patients. 192 RA patients and 278 age-matched healthy controls were included. Clinical and laboratory data were registered. We analyzed a total of 12 SNPs in STAT4, IL10, PSORS1C1, PTPN2, ERAP1, TRAF3IP2 and MIR146A genes by allelic discrimination assays. Case-control association studies and genotype/phenotype correlation analyses were performed. A higher risk to develop RA was observed for rs7574865 in STAT4 gene, while the rs1800872 in IL10 gene showed a protective effect. The presence of RF resulted significantly associated with rs1800872 variant in IL10 while rs2910164 in MIR146A was protective. ACPA were significantly associated with rs7574865 in STAT4. The SNP rs2233945 in PSORS1C1 gene was protective regarding the presence of bone erosions while rs2542151 in PTPN2 gene was associated with joint damage. Our results confirm that polymorphisms in STAT4 and IL10 genes confer susceptibility to RA. For the first time we described that SNPs in PSORS1C1, PTPN2 and MIR146A genes were differently associated with a severe disease phenotype in terms of autoantibody status and radiographic damage in an Italian RA population. This article is protected by copyright. All rights reserved.