Abstract: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 pat… Show more
“…The Gilbert genotype influenced both the prevalence of cholelithiasis and the age at which it developed in patients with thalassemia major [30], whereas it may be a risk factor for symptomatic gallstones in older people with sickle cell disease [13]. Finally patients with CF and gallstones were found to be significantly more likely to carry at least one Gilbert UGT1A1 allele compared with stone-free patients [42].…”
“…The Gilbert genotype influenced both the prevalence of cholelithiasis and the age at which it developed in patients with thalassemia major [30], whereas it may be a risk factor for symptomatic gallstones in older people with sickle cell disease [13]. Finally patients with CF and gallstones were found to be significantly more likely to carry at least one Gilbert UGT1A1 allele compared with stone-free patients [42].…”
“…In fact, gallstones are frequent in CF patients and generally are 'black' pigment, i.e. composed of calcium bilirubinate with an appreciable cholesterol admixture, [8,9] but rarely cause symptoms.…”
“…[45,46] In patients with chronic haemolytic anaemia and cystic fibrosis, promoter polymorphisms of UGT1A1 were associated with an increased gallstone risk underscoring the concept of a genetically determined reduced UDP-glycuronosyl-transferase activity as an important modifier in pigment gallstone formation. [47] Another persuasive example of an oligogenic predisposition to gallstone formation is the low phospholipid-associated cholelithiasis (LPAC) syndrome. In this syndrome, mutations in the ABCB4 gene that encodes the apical phospholipids transporter of hepatocytes are associated with a low phospholipid concentration in bile, intrahepatic gallstones in younger patients, stone recurrence after cholecystectomy and a positive family history for gallstones and intrahepatic cholestasis of pregnancy.…”
Section: Genetic Background Of Gallstone Susceptibilitymentioning
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