Bitte benutzen Sie diese Referenz, um auf diese Ressource zu verweisen: doi:10.22028/D291-41166
Titel: Common variant p.D19H of the hepatobiliary sterol transporter ABCG8 increases the risk of gallstones in children
VerfasserIn: Krawczyk, Marcin
Niewiadomska, Olga
Jankowska, Irena
Jankowski, Krzysztof
Więckowski, Sebastian
Lebensztejn, Dariusz
Więcek, Sabina
Gozdowska, Jolanta
Kułaga, Zbigniew
Weber, Susanne N.
Lütjohann, Dieter
Lammert, Frank
Socha, Piotr
Sprache: Englisch
Titel: Liver International
Bandnummer: 42
Heft: 7
Seiten: 1585-1592
Verlag/Plattform: Wiley
Erscheinungsjahr: 2022
Freie Schlagwörter: cholesterol
gallstone disease
Gilbert syndrome
sterols
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Introduction Gallstones are increasingly common in children. Genetic analyses of adult cohorts demonstrated that the sterol transporter ABCG8 p.D19H and Gilbert UGT1A1*28 variants enhance the odds of developing gallstones. The genetic background of common lithiasis in children remains unknown. Methods Overall, 214 children with gallstone disease (1 month–17 years, 107 boys) were inclueded. The control cohorts comprised 214 children (age 6–17 years, 115 boys) and 172 adults (age 40–92 years, 70 men) without gallstones. The ABCG8 p.D19H and UGT1A1*28 polymorphisms as well as ABCB4 (c.504C>T rs1202283, c.711A>T rs2109505) and NPC1L1 variants (p.V1296V rs217434, c.−18C>A rs41279633) were genotyped using TaqMan assays. Serum concentrations of plant sterols and cholesterol precursors were measured by gas chromatography/mass spectrometry. Results The ABCG8 risk allele was associated with an increased risk of stones (OR = 1.82, p = .03). Children carrying the p.19H allele presented with lower serum concentrations of surrogate markers of intestinal cholesterol absorption and decreased ratios of phytosterols to the cholesterol precursor desmosterol. Carriers of the common NPC1L1 rs217434 allele had an increased gallstone risk compared with stone-free adults (OR 1.90, p < .01). This variant also affected the ratio of phytosterols to cholesterol precursors (p = .03). Other tested variants were not associated with gallstone risk. Conclusions The p.D19H ABCG8 and, to a lesser extent, NPC1L1 rs217434 variants increase the risk of early-onset gallstone formation. These results point to the presence of a common lithogenic pathway in children and adults.
DOI der Erstveröffentlichung: 10.1111/liv.15186
URL der Erstveröffentlichung: https://doi.org/10.1111/liv.15186
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-411663
hdl:20.500.11880/36938
http://dx.doi.org/10.22028/D291-41166
ISSN: 1478-3231
1478-3223
Datum des Eintrags: 24-Nov-2023
Bezeichnung des in Beziehung stehenden Objekts: Supporting Information
In Beziehung stehendes Objekt: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fliv.15186&file=liv15186-sup-0001-TableS1-S7.docx
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Innere Medizin
Professur: M - Prof. Dr. Frank Lammert
M - Keiner Professur zugeordnet
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons