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News

Genetic risk factors for stenosis and biliary candida infections in primary sclerosing cholangitis

Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis, reports this month's Alimentary Pharmacology & Therapeutics.

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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.

Dr Gotthardt and colleagues determined 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.

The research team performed a cohort study of 215 patients with PSC treated at our tertiary care center with respect to their rs601338-FUT2 genotype.

Results of endoscopic retrograde cholangiography and bile culture were analyzed.

The researchers obtained 639 biliary samples, cultured and subjected to microbial analysis.

Clinical and laboratory data were analyzed using chart reviews.

32% of patients were found to be wildtype (GG)

Alimentary Pharmacology & Therapeutics

For the rs601338-FUT2 genotype, 32% of patients were found to be wildtype (GG), 45% of patients were heterozygous (AG), and 23% of patients 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.

The research team found that patients with mutated alleles showed an increased frequency of episodes of cholangitis, development of dominant stenosis, and a reduced actuarial transplantation-free survival.

The team observed that levels of biliary Ca19-9 were significantly elevated in the homozygous-mutated patients.

Dr Gotthardt's team concluded, "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."

Aliment Pharmacol Ther 2014: 39(8): 873–882
01 April 2014

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