With the exception of the major histocompatibility complex (MHC) and STAT4, no otherrheumatoid arthritis (RA) linkage peak has been successfully fine-mapped to date.
We have demonstrated associations between JIA and variants in the TNFAIP3, STAT4, and C12orf30 regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus.
Unlike several other risk genes for RA such as PTPN22, PADI4, and FCRL3, a haplotype of the STAT4 gene shows consistent association with RA susceptibility across Whites and Asians, suggesting that this risk haplotype predates the divergence of the major racial groups.
To test the hypothesis that the variant haplotype of STAT4 seen in RA and SLE is also associated with pSS, we genotyped rs7574865, the most strongly disease-associated SNP in the variant STAT4 haplotype, in 124 Caucasian pSS subjects and compared them to 1143 Caucasian controls.
Thus, in addition to the previously associated STAT4 alleles, variants at these three loci may contribute to RA not only among Europeans, but also among Asians.
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.
This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort.
These findings strongly suggest that STAT4 genetic polymorphisms are associated with RA in Northwestern Chinese Han population, and support the hypothesis of STAT4 gene polymorphisms increasing the risk for RA across major populations.
The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis.
The genetic interactions between IRF5 and STAT4 polymorphisms in SLE and RA susceptibility were examined using the epistasis options in PLINK software.
The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin (for T versus G, P = 1.2 x 10(-6), odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.31-1.92), and the association was described for the first time in both clinical forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis (for T versus G, P = 0.006, OR 1.29, 95% CI 1.07-1.55), and in type 1 diabetes mellitus (for T versus G, P = 0.008, OR 1.36, 95% CI 1.07-1.71).
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.
Taking into consideration that different autoimmune diseases may share some common pathogenetic pathways, we hypothesized that STAT4, a susceptibility gene found to be associated with increased risk for systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, Sjögren's syndrome, Wegener's granulomatosis, Crohn's disease, and ulcerative colitis may also have a role in psoriasis.
Sixty-three RA patients were included.Nine genes (13 SNPs) were subsequently analyzed, including those coding for cytokines involved in synovitis (IL10, LTA, TGFβ1, TNF-α, TNF receptor II) and genes associated with RA susceptibility (-C5 TRAF1, STAT4, TNFAIP3 and PTPN22).
Similarly, mutated allele T or genotypes T/T and G/T of the STAT4rs7574865 SNP were also associated with susceptibility to RA (OR=1.9, 95% CI=1.46-2.50, and OR=2.37, 95% CI 1.73-2.25, respectively).
Recently, the association of a common STAT4 haplotype with type 1 diabetes (T1D) as well as rheumatoid arthritis has been documented in Caucasians and Koreans.
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.
Recent studies demonstrated an association of STAT4 variants with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), indicating that multiple autoimmune diseases share common susceptibility genes.
Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility.