Accumulation of Dietary Cholesterol in Sitosterolemia Caused by Mutations in Adjacent ABC Transporters

DOI Web Site 被引用文献81件
  • Knut E. Berge
    Department of Molecular Genetics and McDermott Center for Human Growth and Development and
  • Hui Tian
    Tularik Inc., Two Corporate Drive, South San Francisco, CA 94080, USA.
  • Gregory A. Graf
    Department of Molecular Genetics and McDermott Center for Human Growth and Development and
  • Liqing Yu
    Department of Molecular Genetics and McDermott Center for Human Growth and Development and
  • Nick V. Grishin
    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.
  • Joshua Schultz
    Tularik Inc., Two Corporate Drive, South San Francisco, CA 94080, USA.
  • Peter Kwiterovich
    Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Bei Shan
    Tularik Inc., Two Corporate Drive, South San Francisco, CA 94080, USA.
  • Robert Barnes
    Department of Molecular Genetics and McDermott Center for Human Growth and Development and
  • Helen H. Hobbs
    Department of Molecular Genetics and McDermott Center for Human Growth and Development and

書誌事項

公開日
2000-12
DOI
  • 10.1126/science.290.5497.1771
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:p> 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 <jats:italic>ABCG8</jats:italic> and one in <jats:italic>ABCG5</jats:italic> ) 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. </jats:p>

収録刊行物

  • Science

    Science 290 (5497), 1771-1775, 2000-12

    American Association for the Advancement of Science (AAAS)

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