Meta-analysis reveals an association of STAT4 polymorphisms with systemic autoimmune disorders and anti-dsDNA antibody

Abstract

Signal transducer and activator of transcription 4 (STAT4) has been recently identified as a susceptibility gene for multiple autoimmune diseases. Here we performed a comprehensive analysis of the association between STAT4 and several different autoimmune disorders to identify potential common inflammatory principles behind this association. Our meta-analysis revealed that the STAT4 rs7574865 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. Furthermore, the stratified meta-analysis also demonstrate that the STAT4 rs7574865 polymorphism is associated with the presence of autoantibodies with systemic reactivity (anti-ds-DNA antibodies) in SLE patients (OR=1.37; 95% CI=1.21-1.56, P=1.12×10-6). However, no such specific association was seen in RA with regard to the presence of non-systemically reacting antibodies, including rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Taken together, these results suggest that STAT4 polymorphisms are associated with autoimmune diseases which are characterized by a systemic pathology and anti-dsDNA antibody. © 2013 American Society for Histocompatibility and Immunogenetics.