Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis.
Aliment Pharmacol Ther
; 39(8): 873-82, 2014 Apr.
Article
en En
| MEDLINE
| ID: mdl-24612312
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Candida
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Candidiasis
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Colangitis Esclerosante
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Constricción Patológica
/
Fucosiltransferasas
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Aliment Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2014
Tipo del documento:
Article
País de afiliación:
Alemania