STAT4, a transcription factor transmitting signals induced by several key cytokines, has recently been identified as a genetic risk factor for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's disease (SD), thus indicating that multiple autoimmune diseases may share common biochemical pathways that lead to immune deregulation.
STAT4 is a transcription factor that is activated by IFN-alpha signaling, and genetic variation of STAT4 has been associated with risk of SLE and rheumatoid arthritis.
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.
A haplotype in STAT4 gene associated with rheumatoid arthritis in Caucasians is not associated in the Han Chinese population, but with the presence of rheumatoid factor.
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.
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.
Asian controls have significantly higher allele frequency (32%) for the minor T allele of STAT4rs7574865 SNP than population of European origin (22%), however, there was no significant difference of ORs for RA and SLE by ethnicity.
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.