title: Cystic fibrosis transmembrane conductance regulator gene polymorphisms in patients with primary sclerosing cholangitis.
abstract: OBJECTIVE
  Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease commonly associated with inflammatory bowel disease (IBD) and characterized by fibrosing inflammatory destruction of bile ducts. The histological features in the liver of PSC patients are similar to those observed in cystic fibrosis (CF). Our aim was to study whether variants in the CFTR gene are associated with the occurrence and/or evolution of PSC.
  
  
  METHODS
  PSC patients (n=140) were genotyped for F508del, the TGmTn variants, and four additional polymorphic loci (1001+11 C>T, M470V, T854T and Q1463Q), and compared to 136 matched healthy controls.
  
  
  RESULTS
  The 1540G-allele, encoding V470, was less frequent in PSC (52%) than in controls (64%, p=0.003), and was associated with protection against PSC in individuals without IBD (OR 0.25, 95% CI 0.12-0.52, p=0.0002). Also TG11-T7 was less frequent in PSC (53%) than in controls (61%, p=0.04), this haplotype was associated with reduced risk for PSC (OR 0.34, 95% CI 0.17-0.70, p=0.003) in individuals without IBD.
  
  
  CONCLUSIONS
  In this cohort of PSC patients, several CFTR-variants affecting the functional properties of the CFTR protein seem to offer protection against the development of PSC, confirming our hypothesis that CFTR might be implicated in the pathogenesis of PSC.
authors.affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Herestraat 49, B-3000 Leuven, Belgium. liesbet.henckaerts@uz.kuleuven.ac.be
authors.forename: Liesbet
authors.initials: L
authors.lastname: Henckaerts
authors.forename: Martine
authors.initials: M
authors.lastname: Jaspers
authors.forename: Werner
authors.initials: W
authors.lastname: Van Steenbergen
authors.forename: Liesbet
authors.initials: L
authors.lastname: Vliegen
authors.forename: Johan
authors.initials: J
authors.lastname: Fevery
authors.forename: Hilde
authors.initials: H
authors.lastname: Nuytten
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Cassiman
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Harry
authors.initials: H
authors.lastname: Cuppens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015209:Cholangitis, Sclerosing / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator