title: Potential role for the common cystic fibrosis DeltaF508 mutation in Crohn's disease.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) is an epithelial barrier disease that is thought to result from a dysregulated interaction with bacteria in the intestine of genetically predisposed individuals. The cystic fibrosis transmembrane conductance regulator (CFTR), which is mutated in the autosomal recessive disease cystic fibrosis, modulates gut permeability, mucus production, and epithelial interactions with bacteria. The cystic fibrosis DeltaF508 mutation is commonly found in the general population and has been shown to result in a reduced number of CFTR molecules at the surface of epithelial cells. Given the important biological functions of CFTR in the intestine, we tested whether this mutation is of relevance to IBD.
  
  
  METHODS
  Using DNA heteroduplex analysis, we investigated the distribution of DeltaF508 heterozygosity in 2568 subjects from three independent cohorts of Italian, Swedish, and Scottish IBD patients and controls.
  
  
  RESULTS
  In all three cohorts an association between DeltaF508 and Crohn's disease (CD) was observed. Specifically, DeltaF508 heterozygosity was markedly underrepresented in CD patients from Italy and Sweden (P = 0.021 and 0.027 versus controls, respectively), while stratification for disease location revealed an absence of DeltaF508 carriers among Scottish CD patients with right-sided colitis (P = 0.023 versus all other locations).
  
  
  CONCLUSIONS
  DeltaF508 heterozygosity might exert a protective effect in CD.
authors.affiliation: Strategic Research Center IRIS, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bresso
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.forename: Marco
authors.initials: M
authors.lastname: Astegiano
authors.forename: Brunello
authors.initials: B
authors.lastname: Demarchi
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Sapone
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Paolo
authors.initials: P
authors.lastname: Gionchetti
authors.forename: Karen M
authors.initials: KM
authors.lastname: Lammers
authors.forename: Annalisa
authors.initials: A
authors.lastname: de Leone
authors.forename: Gabriele
authors.initials: G
authors.lastname: Riegler
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Nimmo
authors.forename: Hazel
authors.initials: H
authors.lastname: Drummond
authors.forename: Colin
authors.initials: C
authors.lastname: Noble
authors.forename: Leif
authors.initials: L
authors.lastname: Torkvist
authors.forename: Anders
authors.initials: A
authors.lastname: Ekbom
authors.forename: Marco
authors.initials: M
authors.lastname: Zucchelli
authors.forename: Robert
authors.initials: R
authors.lastname: Lofberg
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
authors.forename: Sven
authors.initials: S
authors.lastname: Pettersson
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
mesh_terms: D000293:Adolescent; D000328:Adult; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000502:physiology; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012606:Scotland; D013548:Sweden
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator