{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:19:48Z","timestamp":1792430388953,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T00:00:00Z","timestamp":1588723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2013.144.1"],"award-info":[{"award-number":["2013.144.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease without a curative medical therapy. The human UDP\u2010glucuronosyltransferases 1A play a major role in the detoxification and elimination of bilirubin, bile acids and xenobiotics. Whether genetic UGT1A variants determine course and outcome of PSC has not yet been described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A large cohort of German PSC patients with a long\u2010term\u2010follow\u2010up was genotyped for UGT1A variants including <jats:italic>UGT1A1*28<\/jats:italic>, <jats:italic>UGT1A3<\/jats:italic>\u201066 T&gt;C and <jats:italic>UGT1A7 p.N129K\/p.R131K<\/jats:italic> using TaqMan 5'\u2010nuclease assays. Results were correlated with clinical characteristics and transplant\u2010free survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>About 331 patients with PSC were included in the study (69.9% male, mean age at diagnosis 32.6\u00a0years). Median transplant\u2010free survival was 14.9 years. Patients with wild\u2010type alleles of all three <jats:italic>UGT1A<\/jats:italic> genes had a longer transplant\u2010free survival (17.2 vs. 14.4\u00a0years, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.048) than patients carrying a homozygous or heterozygous SNP variant in at least one of the <jats:italic>UGT1A1, UGT1A3<\/jats:italic> or <jats:italic>UGT1A7<\/jats:italic> genes. Additionally, we found that patients carrying wild\u2010type alleles of all three <jats:italic>UGT1A<\/jats:italic> genes had lower serum bilirubin (25 vs. 38\u00a0\u00b5mol\/L, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02) and serum cholesterol (195 vs. 223\u00a0mg\/dL), <jats:italic>P<\/jats:italic>\u00a0=\u00a0.035) at first presentation. Furthermore, inflammatory bowel disease was found to be associated with wild\u2010type <jats:italic>UGT1A<\/jats:italic> alleles (82.2% vs. 68.4%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.046).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This large cohort shows an association with single nucleotide polymorphisms of the <jats:italic>UGT1A1<\/jats:italic>, <jats:italic>UGT1A3<\/jats:italic> and <jats:italic>UGT1A7<\/jats:italic> genes and outcome in PSC. Thus, <jats:italic>UGT1A<\/jats:italic> variants may represent a tool for the prognostic stratification of PSC patients and establish a link between disease progression and the regulation of detoxification by glucuronidation in PSC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14487","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T05:55:58Z","timestamp":1587707758000},"page":"1645-1654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic variants of <i>UDP\u2010glucuronosyltransferase 1A<\/i> genes are associated with disease presentation and outcome in primary sclerosing cholangitis"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9736-1483","authenticated-orcid":false,"given":"Tobias J.","family":"Weism\u00fcller","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 1 University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-5818","authenticated-orcid":false,"given":"Taotao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 1 University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Kalthoff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 1 University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrike","family":"Lenzen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen University of Duisburg\u2010Essen Essen Germany"},{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Manns","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-5359","authenticated-orcid":false,"given":"Christian P.","family":"Strassburg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 1 University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.07.022"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2011.10.003"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000052"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.11.046"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27744"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.11.026"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.009"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.061133"},{"key":"e_1_2_8_10_1","unstructured":"StrassburgCP KalthoffS.Coffee and Gastrointestinal Glucuronosyltransferases. 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