{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:43:31Z","timestamp":1791139411297,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,3,31]],"date-time":"2014-03-31T00:00:00Z","timestamp":1396224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health, Labour, and Welfare of Japan"},{"name":"National Hospital Organization of Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,3]]},"abstract":"Abstract<\/jats:title>Background & Aims<\/jats:title>Injury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC<\/jats:styled-content>). We therefore examined choline\/phospholipid metabolism in livers of patients with PBC<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Hepatic levels of mRNA<\/jats:styled-content> encoded by choline metabolism\u2010related genes in early stage PBC<\/jats:styled-content> patients were quantified by real\u2010time RT<\/jats:styled-content>\u2010PCR<\/jats:styled-content>. Serum cholesterol and triglyceride concentrations in each lipoprotein compartment and serum\/tissue choline levels were also measured. OCT<\/jats:styled-content>1 expression was quantified by genotype (rs683369 and rs622342).<\/jats:p><\/jats:sec>Results<\/jats:title>Serum choline concentrations were significantly higher in PBC<\/jats:styled-content> patients than in normal individuals, with the concentrations in the former lowered by treatment with fibrates. Hepatic choline levels were markedly lower in PBC<\/jats:styled-content> patients than in controls. The levels of expression of genes associated with choline uptake (OCT<\/jats:styled-content>1 and CTL<\/jats:styled-content>1), phosphatidylcholine synthesis (PEMT<\/jats:styled-content> and BHMT<\/jats:styled-content>), and phosphatidylcholine transport (MDR<\/jats:styled-content>3) were significantly upregulated in PBC<\/jats:styled-content> compared with control livers. Serum cholesterol concentrations and the cholesterol\/triglyceride ratio in serum very low density lipoprotein were markedly higher in PBC<\/jats:styled-content> patients than in controls. In PBC<\/jats:styled-content> liver, OCT<\/jats:styled-content>1 protein levels were lower in patients with minor (CG<\/jats:styled-content>\/GG<\/jats:styled-content> at rs683369 and\/or CC<\/jats:styled-content> at rs622342) than major (CC<\/jats:styled-content> at rs683369 and AA<\/jats:styled-content> at rs622342) genotypes of the OCT<\/jats:styled-content>1 gene.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>During early stage PBC<\/jats:styled-content>, hepatocellular choline uptake and PC<\/jats:styled-content> synthesis become dysregulated. OCT<\/jats:styled-content>1 genotypes may influence the pathogenesis of PBC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12526","type":"journal-article","created":{"date-parts":[[2014,3,12]],"date-time":"2014-03-12T15:47:09Z","timestamp":1394639229000},"page":"1095-1102","source":"Crossref","is-referenced-by-count":16,"title":["Pathophysiological analysis of primary biliary cirrhosis focusing on choline\/phospholipid metabolism"],"prefix":"10.1111","volume":"35","author":[{"given":"Motoyuki","family":"Kohjima","sequence":"first","affiliation":[{"name":"Department of Gastroenterology National Hospital Organization Kyushu Medical Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munechika","family":"Enjoji","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Hospital Organization Kyushu Medical Center Fukuoka Japan"},{"name":"Health Care Center Fukuoka University Fukuoka 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