title: Macrophage migration inhibitory factor (MIF) -173G/C promoter polymorphism influences upper gastrointestinal tract involvement and disease activity in patients with Crohn's disease.
abstract: BACKGROUND
  Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with increased expression in inflammatory bowel disease. The aim of the study was to analyze the role of the MIF -173G/C single nucleotide polymorphism in Crohn's disease (CD).
  
  
  METHODS
  Using restriction fragment length polymorphism analysis, genomic DNA of 198 patients with CD and 159 unrelated controls was analyzed for the -173G/C SNP in the MIF promoter region. Colonic MIF mRNA expression was measured by quantitative polymerase chain reaction (PCR), serum MIF levels by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Thirty-six of the 146 G/G wildtype carriers (24.7%) but only 3 of the 45 G/C heterozygotes (6.7%) and only 1 of the C/C homozygotes (14.3%) were diagnosed with upper gastrointestinal tract involvement (P = 0.009, odds ratio [OR] = 0.22, 95% confidence interval [CI], 0.06-0.75 for wildtype versus hetero- and homozygous carriers). This result was confirmed in a second prospective study, in which all patients diagnosed with upper gastrointestinal involvement (n = 13) were G/G wildtype carriers (P = 0.01 versus controls). All patients (n = 12; 100%) with a Crohn's disease activity index (CDAI) > 300 were G/G wildtype carriers compared to only 65.6% wildtype carriers in the group with a CDAI < 150 (P = 0.016). MIF is expressed in the colonic mucosa of CD patients and intestinal epithelial cells but its mRNA expression does not correlate with the degree of inflammation and is not upregulated by proinflammatory cytokines. In CD, MIF serum levels are not influenced by the MIF -173G/C polymorphism.
  
  
  CONCLUSIONS
  The MIF -173G/C polymorphism appears to be a factor contributing to a particular CD phenotype characterized by protection against upper gastrointestinal tract involvement and severe disease activity.
authors.affiliation: Department of Medicine II - Grosshadern, University of Munich, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Dambacher
authors.forename: Tanja
authors.initials: T
authors.lastname: Staudinger
authors.forename: Julia
authors.initials: J
authors.lastname: Seiderer
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Sisic
authors.forename: Fabian
authors.initials: F
authors.lastname: Schnitzler
authors.forename: Simone
authors.initials: S
authors.lastname: Pfennig
authors.forename: Katrin
authors.initials: K
authors.lastname: Hofbauer
authors.forename: Astrid
authors.initials: A
authors.lastname: Konrad
authors.forename: Cornelia
authors.initials: C
authors.lastname: Tillack
authors.forename: Jan-Michel
authors.initials: JM
authors.lastname: Otte
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Thomas
authors.initials: T
authors.lastname: Ochsenkühn
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
mesh_terms: D000293:Adolescent; D000328:Adult; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D041742:Upper Gastrointestinal Tract / Q000473:pathology*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger