Association between the <i>PTPN22</i> gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: Further support that <i>PTPN22</i> is an autoimmunity gene

TLDR

The PTPN22 gene encodes a protein tyrosine phosphatase that regulates T‑cell and B‑cell activity, and its missense SNP rs2476601 has been linked to several autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, and type 1 diabetes. This study aimed to assess the association of the rs2476601 SNP with rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, and multiple sclerosis in a UK cohort. Researchers genotyped rs2476601 in 886 RA, 661 JIA, 279 psoriasis, 455 PsA, 379 MS patients and 595 healthy controls, and evaluated associations using chi‑square tests in Stata. The SNP was significantly associated with RA (P = 1.8 × 10⁻⁸) and JIA (P = 0.0005), but not with psoriasis, PsA, or MS, confirming a novel link to JIA and reinforcing PTPN22’s role in certain autoimmune diseases.

Abstract

Abstract Objective The protein tyrosine phosphatase N22 ( PTPN22 ) gene exhibits regulatory activities for both T cells and B cells. A missense single‐nucleotide polymorphism (SNP) within this gene (rs2476601) has recently been associated with 4 autoimmune diseases: rheumatoid arthritis (RA), systemic lupus erythematosus, autoimmune thyroid disease, and type 1 diabetes mellitus, all of which are T cell–mediated and associated with the elaboration of autoantibody. The aim of this study was to investigate associations of the missense SNP of PTPN22 in a number of autoimmune diseases in the UK population, including RA, juvenile idiopathic arthritis (JIA), psoriasis, psoriatic arthritis (PsA), and multiple sclerosis (MS), some of which have not been examined previously. Methods The PTPN22 missense SNP was genotyped in 886 RA, 661 JIA, 279 psoriasis, 455 PsA, and 379 MS patients and in 595 healthy controls. Association with the PTPN22 SNP was analyzed by chi‐square test as implemented in Stata software. Results There was a significant association between the PTPN22 SNP and RA ( P = 1.8 × 10 –8 ) and JIA ( P = 0.0005). In contrast, no association with psoriasis, PsA, or MS was detected. Conclusion We replicated the findings of a previous association with RA and identified a novel association with JIA. Together with previous data showing associations with other autoimmune diseases, our findings provide further evidence that the PTPN22 gene plays a role in the pathogenesis of a subgroup of autoimmune diseases.