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Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis
Author(s) -
Rupp C.,
Friedrich K.,
Folseraas T.,
Wannhoff A.,
Bode K. A.,
Weiss K.H.,
Schirmacher P.,
Sauer P.,
Stremmel W.,
Gotthardt D. N.
Publication year - 2014
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12663
Subject(s) - medicine , genotype , gastroenterology , primary sclerosing cholangitis , liver transplantation , allele , risk factor , cholangiography , stenosis , transplantation , biology , genetics , disease , gene
Summary Background A recent genome‐wide association study identified the FUT 2 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. Aim To determine the impact of the rs601338‐ FUT 2 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‐ FUT 2 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‐ FUT 2 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‐ FUT 2 genotype is strongly associated with episodes of cholangitis, fungobilia and the incidence of dominant stenosis, which are three clinical hallmarks of PSC ; FUT 2 is thus an important genetic risk factor for host‐microbial diversity and disease progression in PSC .