title: STAT4: a risk factor for type 1 diabetes?
abstract: Genes and mechanisms involved in autoimmune diseases, affecting approximately 5% of human population, remain still obscure but there is accumulating evidence that common genetic factors might predispose to multiple autoimmune disorders. 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. Here we demonstrate for the first time, in a genetically homogeneous population, the association of the STAT4 rs7574865 G/T polymorphism, which has been shown to be associated with these autoimmune diseases, with susceptibility to type 1 diabetes (T1D). The susceptibility is associated with a significant increase of the frequency of the T allele (p = 0.0012, two-tailed chi(2), OR = 1.94, 95% CI = 1.29-2.91) in this single-nucleotide polymorphism (SNP). We also present an indication for association with Wegener's granulomatosis. These findings suggest that this variant form of STAT4 may have a putative key role in the development of a variety of autoimmune diseases, probably because of signaling defects that it causes in the IL-12 pathway.
authors.affiliation: Medical School, University of Crete, Heraklion, Greece.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Zervou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mamoulakis
authors.forename: Charalampos
authors.initials: C
authors.lastname: Panierakis
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Boumpas
authors.forename: George N
authors.initials: GN
authors.lastname: Goulielmos
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D050797:STAT4 Transcription Factor / Q000235:genetics*; D055815:Young Adult
chemical_list: D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human