Apolipoprotein E*3-Leiden allele results from a partial gene duplication in exon 4
Abstract
The apolipoprotein E3-Leiden variant has been shown to be associated with familial dysbetalipoproteinemia (FD) in a dominant manner (Havekes et al., Hum Genet 1986;73:157-163). Applying the polymerase chain reaction technique, we have cloned and sequenced relevant parts of both APOE alleles of the original proband. In exon 4 of the E*3-Leiden allele a partial gene duplication encompassing 21 nucleotides was found, leading to a tandem repeat of the codons 120-126 or 121-127. Using an E3-Leiden mutation specific oligonucleotide probe, the same mutation was found in two additional independently ascertained FD patients with an E3E3 phenotype based on isoelectric focusing. The E*3-Leiden mutation will be useful in the elucidation of the etiology of dominantly inherited forms of FD.
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ApoE Leiden is characterized by a tandem repetition of amino acids 121-127 and has arginines at both polymorphic sites 112 and 158.
“ApoE Leiden, one of the most thoroughly studied of the rare apoE variants (6, 11, 12), is characterized by the presence of a tandem repetition of amino acids 121-127 and has arginines at both polymorphic sites 112 and 158 (13, 14).”
From Preferential association of apolipoprotein E Leiden with very low density lipoproteins of human plasma. (1993) · cites this paper as [13]
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 [55]
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Analysis of Apolipoprotein E5 Gene from a Patient with Hyperlipoproteinemia1
Tajima, S., Yamamura, T., & Yamamoto, A. (1988) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a122420 · Cited by 42 · see citing works
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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
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Self-citationImpact 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
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- Authors
- van den Maagdenberg, A. M. J. M., de Knijff, P., Stalenhoef, A. F. H., Gevers Leuven, J. A., Havekes, L. M., & Frants, R. R.
- Affiliations
- Radboud University Nijmegen (NL)
- Netherlands Organisation for Applied Scientific Research (NL)
- Leiden University (NL)
- Corresponding author
- Frants, R.R.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1989-12
- Volume
- 165
- Issue
- 2
- Pages
- 851-857
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2004226331
- Cited by
- 57
- References
- 2
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2016: 1 · 2012: 2
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- apolipoprotein E, partial gene duplication, exon 4, familial dysbetalipoproteinemia, dominant inheritance, tandem repeats
- MeSH terms
- Amino Acid Sequence, Apolipoproteins E, Base Sequence, Cloning, Molecular, Exons, Genes, Genes, Dominant, Multigene Family, Humans, Hyperlipoproteinemia Type III, Leukocytes, Molecular Sequence Data, Genetic Variation, Restriction Mapping, Oligonucleotide Probes, Polymerase Chain Reaction, Apolipoprotein E3
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