title: Signal transducer and activator of transcription and the risk of rheumatoid arthritis and thyroid autoimmune disorders.
abstract: OBJECTIVE
  The signal transducer and activator of transcription 4 (STAT4) gene localised on chromosome 2q32.2-q32.3 is known to be essential for mediating responses to interleukin 12 in lymphocytes and regulating the differentiation of T helper cells. The aim of this study was to investigate the role of the STAT4 gene in susceptibility to rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) in Tunisian case control studies.
  
  
  METHODS
  Genotyping of STAT4 rs7574865 single nucleotide polymorphism (SNP) was performed in 140 patients affected with RA, 159 patients affected with AITDs and 200 healthy controls using TaqMan® allelic discrimination assay. Data were analysed by χ2-test, genotype relative risk (GRR) and odds ratio (OR).
  
  
  RESULTS
  Our results revealed that frequencies of the T allele and the T/T genotype were significantly higher among RA patients compared to controls (p=0.008; p=0.003, respectively). However, no significant associations with the risk of autoimmune thyroid diseases were detected. Moreover, the stratification of RA patients subgroups revealed a significant association of both T allele and T/T genotype in patients presented erosion (p=0.003; p=0.004, respectively) as well as anti-cyclic peptides-negative RA (ACPA-) (p=0.002; p=0.0003, respectively). Furthermore, genotypic association was found according to the absence of rheumatoid factor antibody (RF) (p=0.0014). But, no significant differences in allele and genotype frequencies of STAT4 rs7574865 polymorphism were detected according to the presence of another autoimmune disease, nodules and in HLA-DRB1*04 and HLA-DRB1*0404 positive subgroups.
  
  
  CONCLUSIONS
  Our results support involvement of the STAT4 gene in the genetic susceptibility to RA but not to AITDs in the Tunisian population.
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Ben Hamad
authors.forename: F
authors.initials: F
authors.lastname: Cornelis
authors.forename: H
authors.initials: H
authors.lastname: Mbarek
authors.forename: G
authors.initials: G
authors.lastname: Chabchoub
authors.forename: S
authors.initials: S
authors.lastname: Marzouk
authors.forename: Z
authors.initials: Z
authors.lastname: Bahloul
authors.forename: A
authors.initials: A
authors.lastname: Rebai
authors.forename: F
authors.initials: F
authors.lastname: Fakhfakh
authors.forename: H
authors.initials: H
authors.lastname: Ayadi
authors.forename: E
authors.initials: E
authors.lastname: Petit-Teixeira
authors.forename: A
authors.initials: A
authors.lastname: Maalej
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D014416:Tunisia / Q000453:epidemiology
chemical_list: D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human