The recent meta-analysis of GWAS has expanded the total number of RA-associated loci to more than 100, out of which approximately ∼97% (98 variants) loci are located in non-coding regions, and the other ∼3% (3 variants) are in three different non-HLA genes, i.e., TYK2 (Prp1104Ala), IL6R (Asp358Ala), and PTPN22 (Trp620Arg).
Studying the effects of haplotype partitioning methods on the RA-associated genomic results from the North American Rheumatoid Arthritis Consortium (NARAC) dataset.
Overall, these results showed that the PTPN22 +788 G>A polymorphism is not associated with RA susceptibility in western Mexican population, whereas the presence of G/A genotype is associated with increased PTPN22 mRNA expression in RA patients.
In addition to the long-recognized genetic impact of the HLA locus, interferon regulatory factors, PTPN22, STAT4, and NOX have been implicated in pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
More importantly, the in vitro normalization of PTPN22 expression correlates with clinical response to the targeted therapies in a longitudinal RA cohort.
Literature was searched using PubMed, EMBASE, Cochrane Library, Korean scientific database, Chinese medical databases, and the Indian medical database to identify eligible studies for determining the association of PTPN22-1123 and RA risk.
Similarly, heterozygous (GA) or minor (AA) alleles of <i>PTPN22:rs2476601</i> occurred in 29% RA compared to 6% healthy controls (<i>p</i>-values ≤ 0.05; OR = 5.90).
PTPN22 (that encodes a tyrosine phosphatase) has been associated with the development of several autoimmune diseases, including type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus.
A C1858T single nucleotide polymorphism within PTPN22 (which encodes PTPN22<sup>R620W</sup>) is associated with an enhanced susceptibility to multiple autoimmune diseases including type 1 diabetes and rheumatoid arthritis.
Areas covered: This review covers the literature showing how PTPN22 is implicated in signalling pathways involved in the autoimmune and autoinflammatory processes underlying RA.
Altogether, we propose a novel mechanism of action of PTPN22 risk allele through the generation of cytotoxic CD4<sup>+</sup> T cells and identify EOMES<sup>+</sup> CD4<sup>+</sup> T cells as a relevant T-cell subset in RA pathogenesis.
Meta-analysis by autoimmune disease type showed a significant negative association between the PTPN22 788A allele and systemic lupus erythematous (SLE) (p = 001), rheumatoid arthritis (RA) (p = 0.008), ulcerative colitis (UC) (p = 0.016), but not Crohn's disease (CD).
Protective Effect of Pinitol Against Inflammatory Mediators of Rheumatoid Arthritis via Inhibition of Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22).