Apolipoprotein E1 Lys-146----Glu with type III hyperlipoproteinemia.
Abstract
During the screening of samples obtained from 5 individuals with type III hyperlipidemia, we identified a variant of apolipoprotein (apo) E which exhibited a discrepancy in apo E phenotype showing the E3/E1 isoform on isoelectric focusing (IEF) analysis and E3/E3 on gene analysis. Sequence analysis of the DNA of the proband that was amplified by PCR and subcloned, revealed a single substitution of one lysine (AAG) for one glutamic acid (GAG) at position 146, thereby adding two negatively charged units to apo E3. This defect had been described only for apo E1 to date (Mann et al. (1989) Clin. Res. 37, 520A (abstract)). In this case, PCR-mediated site-directed mutagenesis was used to identify the structural alterations forming the abnormal E1 genotype in the proband's family. Purified apo E1 Lys-146----Glu showed less than 10% of binding activity to apo B, E receptor on human skin fibroblasts compared with apo E3. This substitution demonstrates that Lys-146 is essential for the binding of apo E to the receptor.
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Lipid-bound apoE3[K146E] has less than 10% binding capacity to the LDL receptor and HSPG compared with apoE3.
“Lipid-bound apoE3[K146E] had less than 10% binding capacity to the LDL receptor and HSPG compared with apoE3 [34], [35], [36].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [34]
Heterozygosity for apoE3[K146E] with the apoE3 allele results in dominant expression of type III HLP.
“Finally, heterozygosity for the apoE variant apoE3[K146E] with the apoE3 allele resulted in a dominant expression of type III HLP [33], [34], [35].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [34]
All apoE3 variants studied here demonstrate stronger LDL receptor binding compared to wild-type apoE2.
“In contrast, all apoE3 variants studied here demonstrate stronger LDL receptor binding compared to wild-type apoE2 [28], [30], [34], [35].”
From Biophysical Analysis of Apolipoprotein E3 Variants Linked with Development of Type III Hyperlipoproteinemia (2011) · cites this paper as [34]
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Apolipoprotein E: Structure-Function Relationships
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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
A novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy
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Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features
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- Authors
- Moriyama, K., Sasaki, J., Matsunaga, A., Arakawa, F., Takada, Y., Araki, K., Kaneko, S., & Arakawa, K.
- Affiliations
- Fukuoka University (JP)
- Fukuoka City Hospital (JP)
- Corresponding author
- Sasaki, Jun
- Venue
- Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
- Publisher
- Elsevier BV
- Published
- 1992-09
- Volume
- 1128
- Issue
- 1
- Pages
- 58-64
- ISSN
- 0005-2760 (ISSN-L)
- OpenAlex
- W1971583342
- Cited by
- 37
- References
- 2
- Citations by year
- 2025: 1 · 2022: 3 · 2021: 1 · 2016: 1 · 2014: 1
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism (publishedVersion)
- PubMed (publishedVersion)
- 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, type III hyperlipoproteinemia, apolipoprotein E3, genotype-phenotype discrepancy, site-directed mutagenesis, isoelectric focusing, fibroblasts
- MeSH terms
- Adult, Amino Acid Sequence, Apolipoproteins E, Base Sequence, Child, DNA, Female, Glutamates, Genetic Carrier Screening, Humans, Hyperlipoproteinemia Type III, Lysine, Male, Middle Aged, Molecular Sequence Data, Oligodeoxyribonucleotides, Pedigree, Polymorphism, Restriction Fragment Length, Electrophoresis, Gel, Two-Dimensional, Polymerase Chain Reaction, Glutamic Acid, Apolipoprotein E2
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