Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters

K. E. Berge, H. Tian, G. A. Graf, L. Yu, N. V. Grishin, J. Schultz, P. Kwiterovich, B. Shan, R. Barnes, H. H. Hobbs

Research output: Contribution to journalArticle

1215 Citations (Scopus)

Abstract

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 ABCG8 and one in ABCG5) 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.

Original languageEnglish (US)
Pages (from-to)1771-1775
Number of pages5
JournalScience
Volume290
Issue number5497
DOIs
StatePublished - Dec 1 2000

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Dietary Cholesterol
ATP-Binding Cassette Transporters
Sterols
Cholesterol
Intestinal Absorption
Mutation
Hypercholesterolemia
Genes
Intestines
Coronary Artery Disease
Atherosclerosis
Up-Regulation
Adenosine Triphosphate
Gene Expression
Liver
Sitosterolemia
Hepatobiliary Elimination

ASJC Scopus subject areas

  • General

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Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. / Berge, K. E.; Tian, H.; Graf, G. A.; Yu, L.; Grishin, N. V.; Schultz, J.; Kwiterovich, P.; Shan, B.; Barnes, R.; Hobbs, H. H.

In: Science, Vol. 290, No. 5497, 01.12.2000, p. 1771-1775.

Research output: Contribution to journalArticle

Berge, KE, Tian, H, Graf, GA, Yu, L, Grishin, NV, Schultz, J, Kwiterovich, P, Shan, B, Barnes, R & Hobbs, HH 2000, 'Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters', Science, vol. 290, no. 5497, pp. 1771-1775. https://doi.org/10.1126/science.290.5497.1771
Berge, K. E. ; Tian, H. ; Graf, G. A. ; Yu, L. ; Grishin, N. V. ; Schultz, J. ; Kwiterovich, P. ; Shan, B. ; Barnes, R. ; Hobbs, H. H. / Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. In: Science. 2000 ; Vol. 290, No. 5497. pp. 1771-1775.
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AU - Schultz, J.

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AU - Shan, B.

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