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. AIM: 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.
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. AIM: 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: Andreas Wannhoff; Trine Folseraas; Maik Brune; Christian Rupp; Kilian Friedrich; Johannes Knierim; Karl Heinz Weiss; Peter Sauer; Christa Flechtenmacher; Peter Schirmacher; Wolfgang Stremmel; Johannes R Hov; Daniel N Gotthardt Journal: United European Gastroenterol J Date: 2015-04-09 Impact factor: 4.623
Authors: Andreas Wannhoff; Christian Rupp; Kilian Friedrich; Johannes Knierim; Christa Flechtenmacher; Karl Heinz Weiss; Wolfgang Stremmel; Daniel N Gotthardt Journal: Dig Dis Sci Date: 2016-12-09 Impact factor: 3.199
Authors: Christian Rupp; Konrad Alexander Bode; Fadi Chahoud; Andreas Wannhoff; Kilian Friedrich; Karl-Heinz Weiss; Peter Sauer; Wolfgang Stremmel; Daniel Nils Gotthardt Journal: BMC Infect Dis Date: 2014-10-23 Impact factor: 3.090
Authors: Christian Rupp; Konrad Bode; Karl Heinz Weiss; Gerda Rudolph; Janine Bergemann; Petra Kloeters-Plachky; Fadi Chahoud; Wolfgang Stremmel; Daniel Nils Gotthardt; Peter Sauer Journal: Medicine (Baltimore) Date: 2016-03 Impact factor: 1.889