Association of apolipoprotein E genotypes with lipid levels and coronary risk
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Context Previous reviews of associations of apolipoprotein E (apoE) genotype and coronary disease have been dominated by smaller studies that are liable to biases. Objective To reassess associations of apoE genotypes with circulating lipid levels and with coronary risk. Data sources We conducted an updated meta-analysis including both published and previously unreported studies, using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database published between January 1970 and January 2007, reference lists of articles retrieved, and a registry of relevant studies. Study selection Eighty-two studies of lipid levels (86,067 healthy participants) and 121 studies of coronary outcomes (37,850 cases and 82,727 controls) were identified, with prespecified principal focus on studies with at least 1000 healthy participants for lipids and those with at least 500 coronary outcomes. Data extraction Information on genotype frequencies, lipid levels, coronary outcomes, and laboratory and population characteristics were recorded independently by 2 investigators and/or supplied by study investigators. Results In the most extreme comparison, people with the epsilon2/epsilon2 genotype had 1.14 mmol/L (95% confidence interval [CI], 0.87-1.40 mmol/L [44.0 mg/dL; 95% CI; 33.6-51.1 mg/dL]) or about 31% (95% CI, 23%-38%) lower mean low-density lipoprotein cholesterol (LDL-C) values than those with the epsilon4/epsilon4 genotype. There were approximat…
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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 [9]
The ε2 allele is associated with lower levels of plasma cholesterol and LDL cholesterol and higher levels of triglycerides compared with the ε3 allele, whereas the ε4 allele is associated with higher levels of total cholesterol, LDL cholesterol, and triglycerides.
“The ε2 allele is associated with lower levels of plasma cholesterol and LDL cholesterol and higher levels of triglycerides compared with the ε3 allele, whereas the ε4 allele is associated with higher levels of total cholesterol, LDL cholesterol and triglycerides [18,19].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [18]
Bennet et al. showed in a meta-analysis a stepwise increase in risk of ischemic heart disease from ε32 to ε42 to ε33 to ε43 to ε44.
“Bennet et al. showed, in a meta-analysis, a stepwise increase in risk of ischemic heart disease from ε32 to ε42 to ε33 to ε43 to ε44 [18].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [18]
Results for ε22 lacked power due to rarity of this genotype.
“The results for ε22 lacked power due to rarity of this genotype [18].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [18]
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”
APOE has three variants ε2, ε3, and ε4, depending on different amino acids at positions 112 and 158, and APOE ε3 is regarded as the wild type.
“APOE has three variants ε2, ε3, and ε4, depending on the different amino acids at positions 112 and 158, and the APOE ε3 is regarded as the wild type (Bennet et al., 2007).”
From Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by <i>APOE</i> mutations (2020) · cites this paper as Bennet et al., 2007
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- Authors
- Bennet, A. M., Di Angelantonio, E., Ye, Z., Wensley, F., Dahlin, A., Ahlbom, A., Keavney, B., Collins, R., Wiman, B., de Faire, U., & Danesh, J.
- Affiliations
- University of Cambridge (GB)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2007-09-19
- Volume
- 298
- Issue
- 11
- Pages
- 1300
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2106611664
- Cited by
- 794
- References
- 4
- Citations by year
- 2026: 15 · 2025: 31 · 2024: 41 · 2023: 24 · 2022: 47 · 2021: 44 · 2020: 31 · 2019: 34 · 2018: 45 · 2017: 41 · 2016: 53 · 2015: 45 · 2014: 47 · 2013: 46 · 2012: 49
- FWCI
- 45.80
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- apolipoprotein E, APOE genotype, coronary artery disease, LDL cholesterol, HDL cholesterol, triglycerides, circulating lipids, coronary heart disease risk, genetic association, ε4 allele, genetic polymorphism, serum lipids, meta-regression, heterogeneous effects, publication bias
- MeSH terms
- Apolipoproteins E, Coronary Disease, Genotype, Humans, Lipids, Cholesterol, LDL, Risk Assessment
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