{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:47:05Z","timestamp":1788306425375,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005690","name":"Universit\u00e4t des Saarlandes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005690","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Gallstones are increasingly common in children. Genetic analyses of adult cohorts demonstrated that the sterol transporter <jats:italic>ABCG8<\/jats:italic> p.D19H and Gilbert <jats:italic>UGT1A1*28<\/jats:italic> variants enhance the odds of developing gallstones. The genetic background of common lithiasis in children remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Overall, 214 children with gallstone disease (1\u00a0month\u201317\u00a0years, 107 boys) were inclueded. The control cohorts comprised 214 children (age 6\u201317\u00a0years, 115 boys) and 172 adults (age 40\u201392\u00a0years, 70 men) without gallstones. The <jats:italic>ABCG8<\/jats:italic> p.D19H and <jats:italic>UGT1A1*28<\/jats:italic> polymorphisms as well as <jats:italic>ABCB4<\/jats:italic> (c.504C&gt;T rs1202283, c.711A&gt;T rs2109505) and <jats:italic>NPC1L1<\/jats:italic> variants (p.V1296V rs217434, c.\u221218C&gt;A rs41279633) were genotyped using TaqMan assays. Serum concentrations of plant sterols and cholesterol precursors were measured by gas chromatography\/mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic>ABCG8<\/jats:italic> risk allele was associated with an increased risk of stones (OR\u00a0=\u00a01.82, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.03). 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 <jats:italic>NPC1L1<\/jats:italic> rs217434 allele had an increased gallstone risk compared with stone\u2010free adults (OR 1.90, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01). This variant also affected the ratio of phytosterols to cholesterol precursors (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.03). Other tested variants were not associated with gallstone risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The p.D19H <jats:italic>ABCG8<\/jats:italic> and, to a lesser extent, <jats:italic>NPC1L1<\/jats:italic> rs217434 variants increase the risk of early\u2010onset gallstone formation. These results point to the presence of a common lithogenic pathway in children and adults.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15186","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T12:22:56Z","timestamp":1644236576000},"page":"1585-1592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Common variant p.<scp>D<\/scp>19<scp>H<\/scp> of the hepatobiliary sterol transporter <scp><i>ABCG8<\/i><\/scp> increases the risk of gallstones in children"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-0777","authenticated-orcid":false,"given":"Marcin","family":"Krawczyk","sequence":"first","affiliation":[{"name":"Department of Medicine II, Saarland University Medical Center Saarland University  Homburg Germany"},{"name":"Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery Medical University of Warsaw  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