Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease

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dc.contributor.authorKrawczyk, Marcin
dc.contributor.authorLuetjohann, Dieter
dc.contributor.authorSchirin Sokhan, Ramin
dc.contributor.authorVillarroel, Luis
dc.contributor.authorNervi, Flavio
dc.contributor.authorPimentel, Fernando
dc.contributor.authorLammert, Frank
dc.contributor.authorFrancisco Miquel, Juan
dc.date.accessioned2024-01-10T12:41:26Z
dc.date.available2024-01-10T12:41:26Z
dc.date.issued2012
dc.description.abstractIn hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Conclusion: Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol GSD. (HEPATOLOGY 2012)
dc.description.funderDFG/Conicyt
dc.description.funderFondecyt
dc.description.funderAlexander von Humboldt Foundation
dc.fechaingreso.objetodigital05-04-2024
dc.format.extent11 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1002/hep.25563
dc.identifier.issn0270-9139
dc.identifier.pubmedidMEDLINE:22213168
dc.identifier.urihttps://doi.org/10.1002/hep.25563
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77416
dc.identifier.wosidWOS:000303049400021
dc.information.autorucMedicina;Miquel J;S/I;72216
dc.information.autorucMedicina;Nervi F ;S/I;99156
dc.information.autorucMedicina;Pimentel F ;S/I;58222
dc.information.autorucMedicina;Villarroel L ;S/I;77182
dc.issue.numero5
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final1517
dc.pagina.inicio1507
dc.publisherWILEY-BLACKWELL
dc.revistaHEPATOLOGY
dc.rightsacceso restringido
dc.subjectSERUM PLANT STEROLS
dc.subjectFATTY LIVER-DISEASE
dc.subjectBILIARY CHOLESTEROL
dc.subjectDIETARY-CHOLESTEROL
dc.subjectCRYSTALLIZATION PATHWAYS
dc.subjectNONCHOLESTEROL STEROLS
dc.subjectSUSCEPTIBILITY FACTOR
dc.subjectABSORPTION
dc.subjectABCG8
dc.subjectMICE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePhytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease
dc.typeartículo
dc.volumen55
sipa.codpersvinculados72216
sipa.codpersvinculados99156
sipa.codpersvinculados58222
sipa.codpersvinculados77182
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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