Apolipoprotein E polymorphism in The Netherlands and its effect on plasma lipid and apolipoprotein levels
Abstract
By isoelectric focusing of delipidated sera followed by immunoblotting we studied the apolipoprotein (apo) E polymorphism in 2018 randomly selected 35-years-old males from three different areas in the Netherlands. Comparison of the APOE allele (E*2, E*3, and E*4) frequencies estimated in this study with those reported for several other population samples showed that there are marked differences between the Dutch population and the populations of Japan, New Zealand, Finland, and the United States. These differences in APOE allele frequencies appeared to be mainly due to differences in frequencies of the E*2 allele (decreased in Japan and Finland; increased in New Zealand) and the E*4 allele (increased in Finland; decreased in Japan and the United States). No difference in APOE allele frequencies was found between the Dutch population and the populations of West Germany and Scotland. Measurements of plasma cholesterol and apo B and E concentrations showed that the E*4 allele is associated with elevated plasma cholesterol and apo B levels and with decreased apo E concentrations, whereas the opposite is true for the E*2 allele. In the Dutch population, the sum of average allelic effects of the common APOE alleles on plasma cholesterol and apo B levels is 6.8% and 14.2%, respectively, of the total population mean. The total average allelic effect on plasma apo E concentrations was more pronounced (50.1%), suggesting that the APOE alleles primarily affect apo E concentrations rather than plasma cholesterol and apo B levels. This hypothesis is sustained by the observation that for plasma apo E levels the genetic variance associated with the APOE gene locus contributed about 18% to the total phenotypic variance. For plasma cholesterol and apo B this contribution was only 1.4% and 2.3% and is relatively low as compared with that reported for other population samples.
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Both the ε2 and the ε4 alleles are associated with unfavorable lipid profiles.
“Both the ε2 and the ε4 alleles are associated with unfavorable lipid profiles [8][9][10][11][12][13].”
From APOE and vascular disease: Sequencing and genotyping in general population cohorts (2023) · cites this paper as [11]
At the level of an individual, the effect of the APOE polymorphism on plasma lipid levels is moderate, but because the polymorphism is common, it contributes substantially to total phenotypic variability in plasma lipid levels in the general population.
“At the level of an individual the effect of the APOE polymorphism on plasma lipid levels is moderate, however since the APOE polymorphism is common, it contributes substantially to the total phenotypic variability in plasma lipid levels in the general population [21,24,58].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [21]
Both APOE ε2 and ε4 alleles are associated with unfavourable lipid profiles.
“Both ɛ2 and ɛ4 alleles are associated with unfavourable lipid profiles,12–19”
ApoE4 is cleared more efficiently, resulting in lower apoE levels and higher cholesterol levels.
“Conversely, apoE4 is cleared more efficiently, resulting in lower apoE levels and higher cholesterol levels [ 3, 4].”
From ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age (2006) · cites this paper as [3]
ApoE2 exhibits lower affinity for the LDL receptor, resulting in slower clearance of apoE and higher plasma apoE levels.
“ApoE2 exhibits lower affinity for the LDL receptor, resulting in slower clearance of apoE and higher plasma apoE levels [ 3, 4].”
From ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age (2006) · cites this paper as [3]
Plasma apoE levels are highly dependent on heritable factors.
“Plasma apoE levels are highly dependent on heritable factors [ 3, 24, 25]”
From ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age (2006) · cites this paper as [3]
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“We also observed a trend towards decreased levels of ApoE in plasma from E4 carriers (Table S1), consistent with previous results that observe highest ApoE levels in E2 carriers and lowest in E4 carriers [42,43].”
ResultAPOE and vascular disease: Sequencing and genotyping in general population cohorts
Rasmussen, K. L., Luo, J., Nordestgaard, B. G., Tybjærg-Hansen, A., & Frikke-Schmidt, R. (2023) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2023.117218 · Cited by 22 · see citing works
- Authors
- Smit, M., de Knijff, P., Rosseneu, M., Bury, J., Klasen, E., Frants, R., & Havekes, L.
- Affiliations
- Leiden University (NL)
- AZ Sint-Jan (BE)
- Netherlands Organisation for Applied Scientific Research (NL)
- Venue
- Human Genetics
- Published
- 1988-11
- Volume
- 80
- Issue
- 3
- Pages
- 287-292
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- OpenAlex
- W1966433708
- Cited by
- 127
- References
- 4
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- 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
- APOE polymorphism, APOE alleles, allele frequency variation, serum cholesterol, apolipoprotein B, allelic effects, genetic variance, Dutch population, population comparison
- MeSH terms
- Adult, Alleles, Apolipoproteins B, Apolipoproteins E, Cholesterol, Gene Frequency, Humans, Lipids, Male, Polymorphism, Genetic, Triglycerides
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