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Cited by 1,433Cholesterol and Lipid MetabolismDrug Transport and Resistance MechanismsLipoproteins and Cardiovascular Health

Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1

Rust, Stephan, Rosier, Marie, Funke, Harald, Real, José, Amoura, Zahir, Piette, Jean-Charles, Deleuze, Jean-Francois, Brewer, H. Bryan +3 more·1999·Nature Genetics
DOI 10.1038/11921
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Abstract

Tangier disease (TD) was first discovered nearly 40 years ago in two siblings living on Tangier Island. This autosomal co-dominant condition is characterized in the homozygous state by the absence of HDL-cholesterol (HDL-C) from plasma, hepatosplenomegaly, peripheral neuropathy and frequently premature coronary artery disease (CAD). In heterozygotes, HDL-C levels are about one-half those of normal individuals. Impaired cholesterol efflux from macrophages leads to the presence of foam cells throughout the body, which may explain the increased risk of coronary heart disease in some TD families. We report here refining of our previous linkage of the TD gene to a 1-cM region between markers D9S271 and D9S1866 on chromosome 9q31, in which we found the gene encoding human ATP cassette-binding transporter 1 (ABC1). We also found a change in ABC1 expression level on cholesterol loading of phorbol ester-treated THP1 macrophages, substantiating the role of ABC1 in cholesterol efflux. We cloned the full-length cDNA and sequenced the gene in two unrelated families with four TD homozygotes. In the first pedigree, a 1-bp deletion in exon 13, resulting in truncation of the predicted protein to approximately one-fourth of its normal size, co-segregated with the disease phenotype. An in-frame insertion-deletion in exon 12 was found in the second family. Our findings indicate that defects in ABC1, encoding a member of the ABC transporter superfamily, are the cause of TD.

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  • Defects in the ABCA1 gene cause Tangier disease, characterized by HDL deficiency in plasma, accumulation of cholesteryl esters in lymphatic tissue, peripheral neuropathy, and increased risk for cardiovascular disease.

    “Defects in the ABCA1 gene cause Tangier disease, which is characterized by HDL deficiency in plasma, accumulation of cholesteryl esters in lymphatic tissue, peripheral neuropathy, and an increased risk for cardiovascular disease (Bodzioch et al., 1999; Brooks-Wilson et al., 1999; Rust et al., 1999).”

    From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Rust et al., 1999

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Authors
Rust, S., Rosier, M., Funke, H., Real, J., Amoura, Z., Piette, J.-C., Deleuze, J.-F., Brewer, H. B., Duverger, N., Denèfle, P., & Assmann, G.
Affiliations
  • University of Münster (DE)
  • Pitié-Salpêtrière Hospital (FR)
  • National Institutes of Health (US)
Corresponding author
Rust, Stephan
ORCID
Amoura, Zahir
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
1999-08
Volume
22
Issue
4
Pages
352-355
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/11921
OpenAlex
W1591670239
Cited by
1,433
References
1
Citations by year
2026: 7 · 2025: 18 · 2024: 17 · 2023: 16 · 2022: 23 · 2021: 16 · 2020: 19 · 2019: 21 · 2018: 36 · 2017: 34 · 2016: 27 · 2015: 35 · 2014: 44 · 2013: 41 · 2012: 41
FWCI
119.67
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
Tangier disease, ABCA1 gene, cholesterol efflux, macrophages, foam cells, coronary artery disease, genetic linkage, gene mapping, truncating mutations, insertion-deletion mutations, autosomal recessive inheritance, THP-1 macrophages
MeSH terms
Amino Acid Sequence, Apolipoproteins E, Base Sequence, Chromosomes, Human, Pair 9, Exons, Female, Genetic Markers, Glycoproteins, Humans, Lipoproteins, HDL, Male, Models, Biological, Models, Genetic, Molecular Sequence Data, Mutation, Pedigree, Tangier Disease, Gene Library, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter 1

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