{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699995280470656.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1126/science.290.5497.1771"}},{"identifier":{"@type":"URI","@value":"https://www.science.org/doi/pdf/10.1126/science.290.5497.1771"}},{"identifier":{"@type":"NAID","@value":"80012263712"}}],"dc:title":[{"@value":"Accumulation of Dietary Cholesterol in Sitosterolemia Caused by Mutations in Adjacent ABC Transporters"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n            In healthy individuals, acute changes in cholesterol intake produce modest changes in plasma cholesterol levels. A striking exception occurs in sitosterolemia, an autosomal recessive disorder characterized by increased intestinal absorption and decreased biliary excretion of dietary sterols, hypercholesterolemia, and premature coronary atherosclerosis. We identified seven different mutations in two adjacent, oppositely oriented genes that encode new members of the adenosine triphosphate (ATP)–binding cassette (ABC) transporter family (six mutations in\n            <jats:italic>ABCG8</jats:italic>\n            and one in\n            <jats:italic>ABCG5</jats:italic>\n            ) in nine patients with sitosterolemia. The two genes are expressed at highest levels in liver and intestine and, in mice, cholesterol feeding up-regulates expressions of both genes. These data suggest that ABCG5 and ABCG8 normally cooperate to limit intestinal absorption and to promote biliary excretion of sterols, and that mutated forms of these transporters predispose to sterol accumulation and atherosclerosis.\n          </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381699995280470658","@type":"Researcher","foaf:name":[{"@value":"Knut E. Berge"}],"jpcoar:affiliationName":[{"@value":"Department of Molecular Genetics and McDermott Center for Human Growth and Development and"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470401","@type":"Researcher","foaf:name":[{"@value":"Hui Tian"}],"jpcoar:affiliationName":[{"@value":"Tularik Inc., Two Corporate Drive, South San Francisco, CA 94080, USA."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470272","@type":"Researcher","foaf:name":[{"@value":"Gregory A. Graf"}],"jpcoar:affiliationName":[{"@value":"Department of Molecular Genetics and McDermott Center for Human Growth and Development and"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470656","@type":"Researcher","foaf:name":[{"@value":"Liqing Yu"}],"jpcoar:affiliationName":[{"@value":"Department of Molecular Genetics and McDermott Center for Human Growth and Development and"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470274","@type":"Researcher","foaf:name":[{"@value":"Nick V. Grishin"}],"jpcoar:affiliationName":[{"@value":"Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390–9046, USA."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470273","@type":"Researcher","foaf:name":[{"@value":"Joshua Schultz"}],"jpcoar:affiliationName":[{"@value":"Tularik Inc., Two Corporate Drive, South San Francisco, CA 94080, USA."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470400","@type":"Researcher","foaf:name":[{"@value":"Peter Kwiterovich"}],"jpcoar:affiliationName":[{"@value":"Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470657","@type":"Researcher","foaf:name":[{"@value":"Bei Shan"}],"jpcoar:affiliationName":[{"@value":"Tularik Inc., Two Corporate Drive, South San Francisco, CA 94080, USA."}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470528","@type":"Researcher","foaf:name":[{"@value":"Robert Barnes"}],"jpcoar:affiliationName":[{"@value":"Department of Molecular Genetics and McDermott Center for Human Growth and Development and"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995280470529","@type":"Researcher","foaf:name":[{"@value":"Helen H. Hobbs"}],"jpcoar:affiliationName":[{"@value":"Department of Molecular Genetics and McDermott Center for Human Growth and Development and"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00368075"},{"@type":"EISSN","@value":"10959203"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00368075"}],"prism:publicationName":[{"@value":"Science"}],"dc:publisher":[{"@value":"American Association for the Advancement of Science (AAAS)"}],"prism:publicationDate":"2000-12","prism:volume":"290","prism:number":"5497","prism:startingPage":"1771","prism:endingPage":"1775"},"reviewed":"false","url":[{"@id":"https://www.science.org/doi/pdf/10.1126/science.290.5497.1771"}],"createdAt":"2002-07-27","modifiedAt":"2024-01-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050001201940128768","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Lipid outward translocation by ABC 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Sitosterolaemia"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204432143360","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204433395840","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Current Therapy for Patients with Sitosterolemia –Effect of Ezetimibe on Plant Sterol Metabolism"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204484652800","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"コレステロールの腸管吸収機構"},{"@language":"en","@value":"Mechanisms of Intestinal Cholesterol Absorption"},{"@language":"ja-Kana","@value":"コレステロール ノ チョウカン キュウシュウ キコウ"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204668918656","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Pharmacogenomics in Drug Discovery and Development Research."},{"@value":"医薬品開発研究におけるファーマコゲノミクスの利用"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204868468608","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"A 19-year-old Man with Myocardial Infarction and Sitosterolemia"},{"@value":"Premature Myocardial Infarction: Could I Ask How Old You Are?"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001205179301760","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy","isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Does ABCG2 Need a Heterodimer Partner? 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Sitosterol Analogue on Plasma Lipid Concentrations in Rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679176670848","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@value":"脂質代謝調節の分子基盤"},{"@language":"en","@value":"The Molecular Mechanism of Regulation of Lipid Metabolism"},{"@language":"ja-Kana","@value":"シシツ タイシャ チョウセツ ノ ブンシ キバン"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679248183040","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy","isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"ABC proteins as molecular targets for drug discovery"},{"@language":"ja","@value":"トランスポータ　　研究の最前線　　２　　創薬ターゲットとしてのＡＢＣタンパク質"},{"@value":"創薬ターゲットとしてのABCタンパク質"},{"@language":"ja-Kana","@value":"ソウヤク ターゲット ト シテ ノ ABC タンパクシツ"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679408737152","@type":"Article","resourceType":"学術雑誌論文(journal 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