title: The c.1-260C>T promoter variant of CD14 but not the c.896A>G (p.D299G) variant of toll-like receptor 4 (TLR4) genes is associated with inflammatory bowel disease.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) results from an aberrant immune response to the indigenous intestinal flora in genetically susceptible hosts. Therefore, the study of candidate genes involved in host pathogen interactions is of key interest.
  
  
  METHODS
  In this two-center, retrospective German and Hungarian cohort study, patients with Crohn's disease (CD) (n = 379; German n = 235, Hungarian n = 144) and ulcerative colitis (UC) (n = 263; German n = 145, Hungarian n = 118) and healthy controls (n = 605; German n = 403, Hungarian n = 202) were genotyped for the presence of the CD14 c.1-260C>T promoter variant and the TLR4 c.896A>G (p.D299G) variant by melting curve analysis using fluorescence resonance energy transfer probes. Data were stratified according to the presence of NOD2 (CARD15) mutations and a detailed genotype-phenotype analysis was performed.
  
  
  RESULTS
  In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019). No association of IBD with the TLR4 single-nucleotide polymorphism was found in either cohort (UC p = 0.430, CD p = 0.783 vs. UC p = 0.745, CD p = 0.383).
  
  
  CONCLUSIONS
  IBD appears to be associated with the CD14 c.1-260C>T promoter variant in Germans and Hungarians, but not with the TLR4 c.896A>G (p.D299G) variant.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Charité Medical School, Humboldt University of Berlin, Berlin, Germany. daniel.baumgart@charite.de
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Baumgart
authors.forename: Carsten
authors.initials: C
authors.lastname: Buning
authors.forename: Lars
authors.initials: L
authors.lastname: Geerdts
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Schmidt
authors.forename: Janine
authors.initials: J
authors.lastname: Genschel
authors.forename: Thomas
authors.initials: T
authors.lastname: Fiedler
authors.forename: Enno
authors.initials: E
authors.lastname: Gentz
authors.forename: Tomas
authors.initials: T
authors.lastname: Molnar
authors.forename: Ferenc
authors.initials: F
authors.lastname: Nagy
authors.forename: Janos
authors.initials: J
authors.lastname: Lonovics
authors.forename: Herbert
authors.initials: H
authors.lastname: Lochs
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Renate
authors.initials: R
authors.lastname: Nickel
authors.forename: Heiko
authors.initials: H
authors.lastname: Witt
authors.forename: Axel
authors.initials: A
authors.lastname: Dignass
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4