FUT2 genotype is a risk factor for biliary candida infections and dominant stenosis in primary sclerosing cholangitis
Background and aims: A recent genome-wide association study (GWAS) identified FUT2 secretor status and genotype defined by the single nucleotide polymorphism (SNP) rs601338 as a potential risk factor in primary sclerosing cholangitis (PSC) that significantly influences biliary bacterial composition. We analyzed the impact of FUT2 genotype on clinical significant parameters, including endoscopic finding and fungal infections.
Methods: We analyzed 215 PSC patients that were treated at our tertiary care center with regard to their FUT2 genotype. ERCs and bile culture were analyzed. During ERC 639 biliary cultures were attained and available for microbial analysis. Clinical and laboratory data was obtained by chart review.
Results: 69 patients (32.1%) were wildtype (GG), 97 (45.1%) patients were heterozogous (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 markedly increase of biliary candida infections (p = 0.025). We found a strong effect in patients with mutated alleles on development of dominant stenosis (p < 0.002) and episodes of cholangitis (p = 0.0025). Levels of Ca19 – 9 in bile fluid of homozygous mutated patients were markedly elevated.
Conclusions: FUT2 genotype is strongly associated with dominant stenosis, fungobilia and episodes of cholangitis, three clinical hallmarks of PSC. We conclude that FUT2 displays an important genetic risk factor for host-microbial diversity and risk factor for disease progression in PSC.
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