Apolipoprotein E polymorphism in health and disease
Abstract
Genetic polymorphism of apolipoprotein (apo) E is controlled by three common (epsilon 2, epsilon 2, epsilon 4) and several rare alleles (e.g., epsilon 1, epsilon 4*, epsilon 4v) at the apo E structural gene locus and may be demonstrated by isoelectric focusing of delipidated sera followed by immunoblotting. Apo E allele frequencies vary significantly between different ethnic groups. The common apo E isoforms E2 (arg158----cys) and E4 (cys112----arg) differ functionally from the parent E3 isoform, explaining their effects on the normal variance of plasma lipoprotein concentrations and their association with hyperlipidemic conditions. In all studied populations the receptor-binding defective apo E2 (arg158----cys) is associated with low cholesterol and apo B in heterozygotes and results in primary dysbetalipoproteinemia or type III hyperlipoproteinemia in homozygotes. Conversely, the epsilon 4 allele is associated with high cholesterol in Finns and Germans but less or not significantly so in Japanese or Singapore populations. In addition to their effects on the normal variance of lipoprotein concentrations, the alleles epsilon 2 and epsilon 4 are associated with hypertriglyceridemia and hypercholesterolemia, respectively. A working hypothesis explaining these observations is presented.
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More than 90% of patients with dysbetalipoproteinemia are apoE2 homozygotes.
“More than 90% of patients with dysbetalipoproteinemia2 are apoE2 homozygotes.”
From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [2]
Type III HLP is a multifactorial disease; additional genetic or environmental factors are required for its phenotypic expression.
“This suggests that type III HLP is a multifactorial disease-that is, additional factors, either genetic or environmental, are required for its phenotypic expression.7”
From Severe xanthomatosis associated with familial apolipoprotein E deficiency. (1996) · cites this paper as [7]
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- Authors
- Utermann, G.
- Affiliations
- Universität Innsbruck (AT)
- Corresponding author
- Utermann, Gerd
- Venue
- American Heart Journal
- Publisher
- Elsevier BV
- Published
- 1987-02
- Volume
- 113
- Issue
- 2
- Pages
- 433-440
- ISSN
- 0002-8703 (ISSN-L)
- OpenAlex
- W2000991693
- Cited by
- 389
- References
- 24
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 12 · 2013: 4 · 2012: 3
- FWCI
- 22.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- apolipoprotein E, genetic polymorphism, apolipoprotein E2, APOE ε4, apolipoprotein E3, allele frequency, ethnic differences, hypertriglyceridemia, hypercholesterolemia, type III hyperlipoproteinemia, serum lipoproteins
- MeSH terms
- Alleles, Apolipoproteins E, Ethnicity, Gene Frequency, Humans, Hyperlipoproteinemia Type III, Polymorphism, Genetic
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