Z Gastroenterol 2011; 49 - P2_46
DOI: 10.1055/s-0030-1269563

Serum cholesterol precursors and phytosterol levels indicate increased cholesterol output and biosynthesis as independent predictive risk factors of gallstones

M Krawczyk 1, D Lütjohann 2, R Schirin-Sokhan 3, H Molina 4, L Azocar 4, F Nervi 4, F Lammert 1, JF Miquel 4
  • 1Department of Internal Medicine II, Saarland University Hospital, Homburg, Germany, Homburg
  • 2Department of Clinical Pharmacology, University Hospital Bonn, Bonn
  • 3Department of Medicine III, University Hospital Aachen, Aachen
  • 4Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile

Aims: In enterocytes and hepatocytes sterols transport is mediated by NPC1L1 and ABCG5/8. Whereas serum levels of phytosterol represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect de novo cholesterol synthesis. Here, we compare serum and biliary sterol levels in patients with gallstone disease (GSD) and stone-free controls to determine differences in cholesterol transport and biosynthesis between both groups.

Methods: We studied 112 German patients with GSD and 152 controls as well as two distinct Chilean ethnic groups: Hispanics (100 GSD and 100 controls) and Amerindians (20 GSD and 20 controls). Additionally, an 8-years follow-up of 70 Hispanics of whom 35 developed GSD and 35 remained gallstone-free was performed. Serum sterols were measured by GC-MS. Gallbladder bile sterol levels were analysed in GSD and controls (n=17 each). All individuals were genotyped for the common ABCG5/8 p.Q604E, p.D19H, p.T400K, p.Y54C and p.A632V variants.

Results: GSD patients displayed lower serum levels of phytosterols and higher levels of cholesterol precursors. Phytosterols/cholesterol precursor ratios were significantly lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated. Biliary phytosterol and cholesterol concentrations were 69% and 34% higher, respectively, in GSD patients as compared to controls. Phytosterol levels were significantly lower even before gallstones were detected by ultrasound during follow-up. An ethnic gradient in the phytosterol/cholesterol precursor indixes (Germans > Hispanics > Amerindians) was apparent. Selected ABCG5/8 variants did not show a major effect on serum sterol levels or GSD.

Conclusions: GSD individuals display decreased intestinal cholesterol absorption and increased biliary output, suggesting enhanced whole body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at risk for cholesterol GSD.

(Supported by DFG/CONICYT N°444CHL-113)

cholesterol transport - gallstones - sterols