title: Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis.
abstract: BACKGROUND
  A recent genome-wide association study identified the FUT2 secretor status and genotype defined by the single-nucleotide polymorphism rs601338 as potential genetic risk factor in primary sclerosing cholangitis (PSC), which significantly influences biliary bacterial composition.
  
  
  OBJECTIVE
  To determine the impact of the rs601338-FUT2 genotype on frequency of biliary infections, development of dominant stenosis and liver-transplantation-free survival in patients with PSC.
  
  
  METHODS
  Cohort study of 215 patients with PSC treated at our tertiary care centre with respect to their rs601338-FUT2 genotype. Results of endoscopic retrograde cholangiography and bile culture were analysed; 639 biliary samples were obtained, cultured and subjected to microbial analysis. Clinical and laboratory data were analysed using chart reviews.
  
  
  RESULTS
  For the rs601338-FUT2 genotype, 69 patients (32.1%) were found to be wildtype (GG), 97 (45.1%) patients were heterozygous (AG) and 49 patients (22.8%) were homozygous-mutated (AA). In addition to alterations in the bacterial pattern, especially in heterozygous carriers, patients with mutated alleles had a marked increase in the frequency of biliary Candida infections (P = 0.025). Further, patients with mutated alleles showed an increased frequency of episodes of cholangitis (P = 0.0025), development of dominant stenosis (P < 0.002) and a reduced actuarial transplantation-free survival (P = 0.044). Levels of biliary Ca19-9 were significantly elevated in the homozygous-mutated patients.
  
  
  CONCLUSIONS
  The rs601338-FUT2 genotype is strongly associated with episodes of cholangitis, fungobilia and the incidence of dominant stenosis, which are three clinical hallmarks of PSC; FUT2 is thus an important genetic risk factor for host-microbial diversity and disease progression in PSC.
authors.affiliation: Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rupp
authors.forename: K
authors.initials: K
authors.lastname: Friedrich
authors.forename: T
authors.initials: T
authors.lastname: Folseraas
authors.forename: A
authors.initials: A
authors.lastname: Wannhoff
authors.forename: K A
authors.initials: KA
authors.lastname: Bode
authors.forename: K-H
authors.initials: KH
authors.lastname: Weiss
authors.forename: P
authors.initials: P
authors.lastname: Schirmacher
authors.forename: P
authors.initials: P
authors.lastname: Sauer
authors.forename: W
authors.initials: W
authors.lastname: Stremmel
authors.forename: D N
authors.initials: DN
authors.lastname: Gotthardt
mesh_terms: D000328:Adult; D000483:Alleles; D001646:Bile / Q000382:microbiology; D002175:Candida / Q000302:isolation & purification*; D002177:Candidiasis / Q000453:epidemiology* / Q000209:etiology; D002758:Cholangiography / Q000379:methods; D015209:Cholangitis, Sclerosing / Q000150:complications* / Q000235:genetics / Q000382:microbiology; D015331:Cohort Studies; D003251:Constriction, Pathologic / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase