Common variant p.D19H of the hepatobiliary sterol transporter ABCG8 increases the risk of gallstones in children.
ATP Binding Cassette Transporter, Subfamily G, Member 8
/ genetics
ATP-Binding Cassette Transporters
/ genetics
Adolescent
Adult
Aged
Aged, 80 and over
Child
Cholesterol
Gallstones
/ genetics
Genetic Predisposition to Disease
Humans
Male
Membrane Transport Proteins
/ genetics
Middle Aged
Phytosterols
/ adverse effects
Sterols
/ metabolism
Gilbert syndrome
cholesterol
gallstone disease
sterols
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
revised:
12
11
2021
received:
20
03
2021
accepted:
01
01
2022
pubmed:
8
2
2022
medline:
25
6
2022
entrez:
7
2
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Substances chimiques
ABCG8 protein, human
0
ATP Binding Cassette Transporter, Subfamily G, Member 8
0
ATP-Binding Cassette Transporters
0
Membrane Transport Proteins
0
Phytosterols
0
Sterols
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1585-1592Informations de copyright
© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.
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