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).
Our study confirmed the association of STAT4rs7574865 polymorphism with RA and was the first to indicate an association with RF and anti-CCP antibodies positivity.
An association of STAT4 (rs10181656) with PsA was confirmed whereas CD226 (rs763361) was associated with PsA but not with RA, in contrast to previous reports.
STAT4 variant allele was associated with the absence of a good/moderate EULAR response at 2 years of treatment in the whole RA group and in ETN treated patients.
The aim of this study is to determine the association of the STAT4 polymorphism rs7574865 with RA, disease activity, and anti-cyclic citrullinated peptide (CCP) antibody levels in a Mexican population.
This work aimed at assessing the association of STAT4 G>T gene polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects.
Further work suggested that the BS associated variant of STAT4 is not related to the previously reported one associated with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus.
Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes.
Our meta-analysis revealed that the STAT4rs7574865 polymorphism is associated with four autoimmune diseases with systemic pathology, including systemic lupus erythematosus (OR = 1.52; 95% CI = 1.48 - 1.56, P<1.0 × 10(-16)), rheumatoid arthritis (OR = 1.27; 95% CI = 1.21 - 1.33, P < 1.00 × 10(-16)), systemic sclerosis (OR = 1.38; 95% CI = 1.27 - 1.50, P < 1.44 × 10(-14)), and primary Sjogren's syndrome (OR = 1.32; 95% CI = 1.01 - 1.73, P = 4.40 × 10(-2)), while no association was found with type I diabetes, juvenile idiopathic arthritis, ulcerative colitis and Crohn's disease.
The genetic interactions between IRF5 and STAT4 polymorphisms in SLE and RA susceptibility were examined using the epistasis options in PLINK software.
A significantly increased risk for RA associated with the STAT4rs7574865 TT genotype was evident among older patients and RF-negative patients compared with the STAT4rs7574865 GG genotype.