Coinheritance of Gilbert syndrome-associated UGT1A1 mutation increases gallstone risk in cystic fibrosis.
The prevalence of "black" pigment gallstones is increased in patients with cystic fibrosis (CF). Bile acid malabsorption with augmented bilirubin uptake from the intestine and the development of "hyperbilirubinbilia" have been proposed as key factors in gallstone formation in CF patients. We have now tested the hypothesis that the coinheritance of the common UGT1A1 promoter mutation associated with Gilbert syndrome is an additional lithogenic risk factor for gallstone formation in CF. Our results show that patients with CF and gallstones are significantly more likely to carry at least one Gilbert UGT1A1 allele compared with stone-free patients (OR 7.3; P = .042) and that these carriers display significantly higher serum levels of unconjugated bilirubin (P = .002). In conclusion, the Gilbert UGT1A1 allele increases the risk of gallstone formation in CF. This genetic association supports the current concept for gallstone formation in CF and suggests that genetic and exogenous sources contributing to hyperbilirubinbilia might be lithogenic in CF patients.
Wasmuth
Hermann E
HE
Department of Medicine III, University Hospital Aachen, Aachen University, Aachen, Germany.
Keppeler
Hildegard
H
Herrmann
Ulrike
U
Schirin-Sokhan
Ramin
R
Barker
Michael
M
Lammert
Frank
F
D000293:Adolescent; D000328:Adult; D001663:Bilirubin / Q000097:blood; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000097:blood / Q000235:genetics*; D005260:Female; D042882:Gallstones / Q000097:blood / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005878:Gilbert Disease / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme