Apolipoprotein E1-Hammersmith (Lys146 → Asn;Arg147 → Trp), due to a dinucleotide substitution, is associated with early manifestation of dominant type III hyperlipoproteinaemia
Abstract
Apolipoprotein E (apoE) is one of the major protein constituents of chylomicron and very low density lipoprotein (VLDL) remnants and plays a central role as a ligand in the receptor-mediated uptake of these particles by the liver. Here we describe a new variant of apoE, apoE1-Hammersmith, which is associated with dominantly expressed type III hyperlipidaemia. The propositus, aged 26, developed tubero-eruptive xanthomas at the age of 3, her daughter developed similar lesions at age 7 but her son, aged 3, shows no clinical abnormality so far. All three cases had an apoE3E1 phenotype and a broad beta band on lipoprotein electrophoresis. Cysteamine modification resulted in a shift of apoE1 to the apoE2 isoform position, indicating that the mutation leading to apoE1-Hammersmith occurred on an apoE3 background. ApoE genotyping confirmed these results. Sequence analysis of DNA of the propositus was performed for exons 3 and 4 and revealed a dinucleotide substitution causing two amino acid changes at adjacent positions (Lys146-->Asn) and (Arg147-->Trp).
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APOE1 Hammersmith (Lys146Asn, Arg147Trp) and amino acid 121-127 tandem repeat insertions (APOE3 Leiden) have been reported as causative of dominantly inherited type III HLP.
“In addition, APOE1 Hammersmith (Lys146Asn, Arg147Trp)54) and amino acid 121–127 tandem repeat insertions (APOE3 Leiden)55) have been reported as causative of dominantly inherited type III HLP (Table 2).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [54]
Cites
Apolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830 · see citing works
Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E
Wilson, C., Wardell, M. R., Weisgraber, K. H., Mahley, R. W., & Agard, D. A. (1991) · Science · doi:10.1126/science.2063194 · Cited by 678 · see citing works
Rall, S. C., Weisgraber, K. H., Innerarity, T. L., & Mahley, R. W. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.15.4696 · Cited by 345 · see citing works
Westerlund, J. A., & Weisgraber, K. H. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82318-3 · Cited by 164 · see citing works
de Knijff, P., van den Maagdenberg, A. M., Stalenhoef, A. F., Leuven, J. A., Demacker, P. N., Kuyt, L. P., Frants, R. R., & Havekes, L. M. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115349 · Cited by 100 · see citing works
Self-citationMann, W. A., Lohse, P., Gregg, R. E., Ronan, R., Hoeg, J. M., Zech, L. A., & Brewer, H. B. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118096 · Cited by 28 · see citing works
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Mahley, R. W., Huang, Y., & Rall, S. C. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32417-2 · Cited by 447 · see citing works
APOE gene variants in primary dyslipidemia
Khalil, Y. A., Rabès, J.-P., Boileau, C., & Varret, M. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.05.007 · Cited by 170 · see citing works
Contribution of <i>APOE</i> Genetic Variants to Dyslipidemia
Bea, A. M., Larrea-Sebal, A., Marco-Benedi, V., Uribe, K. B., Galicia-Garcia, U., Lamiquiz-Moneo, I., Laclaustra, M., Moreno-Franco, B., Fernandez-Corredoira, P., Olmos, S., et al. (2023) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.123.318977 · Cited by 40 · see citing works
Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features
Matsunaga, A., & Saito, T. (2025) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.65393 · Cited by 14 · see citing works
Fotakis, P., Vezeridis, A., Dafnis, I., Chroni, A., Kardassis, D., & Zannis, V. I. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m048348 · Cited by 4 · see citing works
- Authors
- Hoffer, M. J. V., Niththyananthan, S., Naoumova, R. P., Kibirige, M. S., Frants, R. R., Havekes, L. M., & Thompson, G. R.
- Affiliations
- Leiden University (NL)
- Hammersmith Hospital (GB)
- Netherlands Organisation for Applied Scientific Research (NL)
- Corresponding author
- Hoffer, Mariëtte J.V
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 124
- Issue
- 2
- Pages
- 183-189
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W2080563134
- Cited by
- 32
- References
- 6
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 1
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- TNO Repository (submittedVersion)
- Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, familial hypercholesterolemia, lipoprotein electrophoresis, VLDL remnants, chylomicrons
- MeSH terms
- Adult, Anticholesteremic Agents, Hypolipidemic Agents, Apolipoproteins E, Child, Child, Preschool, Cholesterol, Cholestyramine Resin, Cysteamine, DNA, Electrophoresis, Exons, Female, Genotype, Humans, Hyperlipoproteinemia Type III, Male, Nuclear Family, Phenotype, Fenofibrate, Radiation-Protective Agents, Triglycerides, Immunoblotting, Point Mutation, Dinucleotide Repeats
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