Genotyping and sequence analysis of apolipoprotein E isoforms*1
Abstract
Apolipoprotein E (apoE), a polymorphic plasma protein, is essential for catabolism of lipoproteins by receptor-mediated endocytosis. One of the apoE isoforms (E2) differs in its binding affinity to specific receptors and contributes to variations in lipoprotein metabolism. Diagnosis of apoE isoforms is done by isoelectric focusing, but it is hindered by various degrees of post-translational sialylation of the apoE protein. Electrophoretically silent structural variations may also escape detection by this technique. We describe a method for genotyping apoE based on hybridization of allele-specific oligonucleotides with enzymatically amplified genomic DNA, which permits unambiguous diagnosis of six common apoE phenotypes within 24 h. Among 100 E2 alleles present in 81 unrelated individuals genotyped by this technique, we found two rare structural mutants of apoE in addition to the common E2 form, E2(158Arg----Cys). Automated sequencing of amplified DNA identified the rare mutants as E2(136Arg----Ser) and E2(145Arg----Cys). The genotypic method may complement or even replace isoelectric focusing for routine determination of apoE phenotypes and for identification of rare structural variants.
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Heterozygosity for apoE2(145 Arg→Cys), apoE2(146 Lys→Gln), or apoE2-Christchurch(136 Arg→Ser) is associated with type III hyperlipoproteinemia.
“While heterozygosity for three further mutants (apoE2(145 Arg→Cys) (32, 33), apoE2(146 Lys→Gln) (34), or apoE2-Christchurch(136 Arg→Ser) (18, 33)) is associated with type III hyperlipoproteinemia, there are no family studies to ascertain whether these variants also demonstrate a dominant mode of inheritance.”
From Apolipoprotein E3-Leiden contains a seven-amino acid insertion that is a tandem repeat of residues 121–127 (1989) · cites this paper as [33]
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- Authors
- EMI, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- EMI, M
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 1988-11
- Volume
- 3
- Issue
- 4
- Pages
- 373-379
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W2058116753
- Cited by
- 301
- References
- 4
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 10 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 10 · 2013: 6 · 2012: 2
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL21088-11)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- apolipoprotein E, APOE isoforms, allele-specific oligonucleotide hybridization, PCR genotyping, sialylation, lipoprotein metabolism, receptor binding affinity
- MeSH terms
- Alleles, Amino Acid Sequence, Apolipoproteins E, Base Sequence, Exons, Genes, Genotype, Humans, Molecular Sequence Data, Mutation, Nucleic Acid Hybridization, Phenotype, Polymorphism, Genetic, Oligonucleotide Probes
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