title: Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset.
abstract: BACKGROUND
  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. We therefore investigated the influence of STAT4 variants on the susceptibility and phenotype of inflammatory bowel diseases (IBD) in a large patient and control cohort.
  
  
  RESULTS
  Genomic DNA from 2704 individuals of Caucasian origin including 857 patients with Crohn's disease (CD), 464 patients with ulcerative colitis (UC), and 1383 healthy, unrelated controls was analyzed for seven SNPs in the STAT4 gene (rs11889341, rs7574865, rs7568275, rs8179673, rs10181656, rs7582694, rs10174238). In addition, a detailed genotype-phenotype analysis was performed. Our analysis revealed an association of the STAT4 SNP rs7574865 with overall decreased susceptibility to CD (p = 0.047, OR 0.86 [95% CI 0.74-0.99]). However, compared to CD patients carrying the wild type genotype, the STAT4 SNP rs7574865 was significantly associated with early CD onset (p = 0.021) and colonic CD (p = 0.008; OR = 4.60, 95% CI 1.63-12.96). For two other STAT4 variants, there was a trend towards protection against CD susceptibility (rs7568275, p = 0.058, OR 0.86 [95% CI 0.74-1.00]; rs10174238, p = 0.057, OR 0.86 [95% CI 0.75-1.00]). In contrast, we did not observe any association with UC susceptibility. Evidence for weak gene-gene interaction of STAT4 with the IL23R SNP rs11209026 was lost after Bonferroni correction.
  
  
  CONCLUSIONS
  Our results identified the STAT4 SNP rs7574865 as a disease-modifying gene variant in colonic CD. However, in contrast to SLE and RA, the effect of rs7574865 on CD susceptibility is only weak.
authors.affiliation: Department of Medicine II-Grosshadern, University of Munich, Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Julia
authors.initials: J
authors.lastname: Seiderer
authors.forename: Melinda
authors.initials: M
authors.lastname: Nagy
authors.forename: Christoph
authors.initials: C
authors.lastname: Fries
authors.forename: Florian
authors.initials: F
authors.lastname: Beigel
authors.forename: Maria
authors.initials: M
authors.lastname: Weidinger
authors.forename: Simone
authors.initials: S
authors.lastname: Pfennig
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klein
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Matthias
authors.initials: M
authors.lastname: Folwaczny
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Thomas
authors.initials: T
authors.lastname: Ochsenkühn
authors.forename: Julia
authors.initials: J
authors.lastname: Diegelmann
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Darina
authors.initials: D
authors.lastname: Roeske
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
mesh_terms: D017668:Age of Onset; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000235:genetics*
chemical_list: C515500:IL23R protein, human; D018123:Receptors, Interleukin; D050797:STAT4 Transcription Factor
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