期刊
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
卷 39, 期 8, 页码 873-882出版社
WILEY
DOI: 10.1111/apt.12663
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资金
- Deutsche Forschungsgemeinschaft
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.
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