Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency
Abstract
Genes have a major role in the control of high-density lipoprotein (HDL) cholesterol (HDL-C) levels. Here we have identified two Tangier disease (TD) families, confirmed 9q31 linkage and refined the disease locus to a limited genomic region containing the gene encoding the ATP-binding cassette transporter (ABC1). Familial HDL deficiency (FHA) is a more frequent cause of low HDL levels. On the basis of independent linkage and meiotic recombinants, we localized the FHA locus to the same genomic region as the TD locus. Mutations in ABC1 were detected in both TD and FHA, indicating that TD and FHA are allelic. This indicates that the protein encoded by ABC1 is a key gatekeeper influencing intracellular cholesterol transport, hence we have named it cholesterol efflux regulatory protein (CERP).
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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 Brooks-Wilson et al., 1999
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- Authors
- Brooks-Wilson, A., Marcil, M., Clee, S. M., Zhang, L.-H., Roomp, K., van Dam, M., Yu, L., Brewer, C., Collins, J. A., Molhuizen, H. O. F., Loubser, O., Ouelette, B. F. F., Fichter, K., Ashbourne-Excoffon, K. J. D., Sensen, C. W., Scherer, S., Mott, S., Denis, M., Martindale, D., Frohlich, J., Morgan, K., Koop, B., Pimstone, S., Kastelein, J. J. P., Genest, J., & Hayden, M. R.
- Affiliations
- University of British Columbia (CA)
- Montreal Clinical Research Institute (CA)
- Montreal General Hospital (CA)
- Amsterdam UMC Location University of Amsterdam (NL)
- Institute for Marine Biosciences (CA)
- University of Toronto (CA)
- University of Victoria (CA)
- Corresponding author
- Hayden, Michael R.
- ORCID
- Venue
- Nature Genetics
- Published
- 1999-08
- Volume
- 22
- Issue
- 4
- Pages
- 336-345
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1860908381
- Cited by
- 1,687
- References
- 4
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 18 · 2023: 20 · 2022: 31 · 2021: 29 · 2020: 26 · 2019: 28 · 2018: 39 · 2017: 34 · 2016: 33 · 2015: 36 · 2014: 57 · 2013: 53 · 2012: 50
- FWCI
- 126.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- Tangier disease, ABC transporters, HDL cholesterol, genetic linkage, allelic mutations, intracellular cholesterol transport, meiotic recombination
- MeSH terms
- Adult, Amino Acid Sequence, Base Sequence, Chromosomes, Human, Pair 9, Female, Genetic Markers, Glycoproteins, Humans, Genetic Linkage, Cholesterol, HDL, Male, Models, Genetic, Molecular Sequence Data, Mutation, Pedigree, Tangier Disease, Sequence Homology, Amino Acid, ATP-Binding Cassette Transporters, Physical Chromosome Mapping, ATP Binding Cassette Transporter 1
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