CoChat
Sign Up
Cited by 1,512Cholesterol and Lipid MetabolismLipid metabolism and disordersDrug Transport and Resistance Mechanisms

The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease

Bodzioch, Marek, Orsó, Evelyn, Klucken, Jochen, Langmann, Thomas, Böttcher, Alfred, Diederich, Wendy, Drobnik, Wolfgang, Barlage, Stefan +9 more·1999·Nature Genetics
DOI 10.1038/11914
Open this paper in CoChat — free account

Abstract

Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors. In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism. HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts, which have a reduced in vitro growth rate. The TD locus has been mapped to chromosome 9q31. Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22-31. We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.

Integrity signals

Registry

Crossref · 10.1038/11914

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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 Bodzioch et al., 1999

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Bodzioch, M., Orsó, E., Klucken, J., Langmann, T., Böttcher, A., Diederich, W., Drobnik, W., Barlage, S., Büchler, C., Porsch-Özcürümez, M., Kaminski, W. E., Hahmann, H. W., Oette, K., Rothe, G., Aslanidis, C., Lackner, K. J., & Schmitz, G.
Affiliations
  • University of Regensburg (DE)
  • University of Cologne (DE)
Corresponding author
Schmitz, Gerd
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
1999-08
Volume
22
Issue
4
Pages
347-351
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/11914
OpenAlex
W1607399348
Cited by
1,512
References
1
Citations by year
2026: 8 · 2025: 14 · 2024: 19 · 2023: 11 · 2022: 25 · 2021: 22 · 2020: 24 · 2019: 24 · 2018: 42 · 2017: 36 · 2016: 28 · 2015: 33 · 2014: 44 · 2013: 40 · 2012: 46
FWCI
122.39
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 › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
Tangier disease, ABC transporters, ABCB4, HDL cholesterol, HDL metabolism, reverse cholesterol transport, mononuclear phagocytes, genetic mutations, premature cardiovascular disease, lipid metabolism disorders
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Base Sequence, Child, Preschool, Chromosomes, Human, Pair 9, Female, Glycoproteins, Humans, Cholesterol, HDL, Male, Middle Aged, Models, Genetic, Molecular Sequence Data, Mutation, Pedigree, Tangier Disease, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review