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Cited by 55Lipoproteins and Cardiovascular HealthGenetic Associations and EpidemiologyParaoxonase enzyme and polymorphisms

ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants

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Kuo, Chia-Ling, Pilling, Luke C., Atkins, Janice L., Kuchel, George A., Melzer, David·2020·Aging
DOI 10.18632/aging.103405PMC PMC7343499

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Abstract

Abstract The Apolipoprotein E (APOE) e4 allele is associated with reduced longevity and increased Coronary Artery Disease (CAD) and Alzheimer’s disease, with e4e4 having markedly larger effect sizes than e3e4. The e2 longevity promoting variant is less studied. We conducted a phenome-wide association study of ApoE e2e3 and e2e2 with aging phenotypes, to assess their potential as targets for anti-aging interventions. Data were from 379,000 UK Biobank participants, aged 40 to 70 years. e2e3 (n=46,535) had mostly lower lipid-related biomarker levels including reduced total and LDL-cholesterol, and lower risks of CAD (Odds Ratio=0.87, 95% CI: 0.83 to 0.90, p=4.92×10 −14 ) and hypertension(OR=0.94, 95% CI: 0.92 to 0.97, p=7.28×10 −7 ) versus e3e3. However, lipid changes in e2e2 (n=2,398) were more extreme, including a marked increase in triglyceride levels (0.41 Standard Deviations, 95% CI: 0.37 to 0.45, p=5.42×10 −92 ), with no associated changes in CAD risks. There were no associations with biomarkers of kidney function. The effects of both e2e2 and e2e3 were minimal on falls, muscle mass, grip strength or frailty. In conclusion, e2e3 has protective effects on some health outcomes, but the effects of e2e2 are not similar, complicating the potential usefulness of e2 as a target for anti-aging intervention.

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  • In the same registries, APOEε2 has been associated with lower LDL cholesterol levels, increased triglyceride levels and increased risk of peripheral vascular disease.

    “By contrast, in the same registries, APOEε2 has been associated with lower LDL cholesterol levels, increased triglyceride levels and increased risk of peripheral vascular disease87,88.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [87]

    The Results (Biomarkers; page unavailable) report lower LDL cholesterol and higher triglycerides for both APOE e2e2 and e2e3 compared with e3e3. The Disease outcomes section does not report an increased risk of peripheral vascular disease, so that part of the claim is unsupported by our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In large health registries such as the UK BioBank, the APOEε4 allele has been associated with higher LDL cholesterol and triglycerides levels, lower HDL cholesterol levels and an increased risk of coronary artery disease.

    “In large health registries such as the UK BioBank, the APOEε4 allele has been associated with higher LDL cholesterol and triglycerides levels, lower HDL cholesterol levels and an increased risk of coronary artery disease.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [87]

    The Abstract in our copy states that APOE ε4 is associated with increased coronary artery disease, and the Methods identify UK Biobank as the study cohort. However, the Results > Biomarkers section reports lipid associations for ε2 genotypes, not ε4; it does not establish the claimed higher LDL and triglycerides or lower HDL for ε4. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Kuo, C.-L., Pilling, L. C., Atkins, J. L., Kuchel, G. A., & Melzer, D.
Affiliations
  • UConn Health (US)
  • University of Exeter (GB)
Corresponding author
Kuo, Chia-Ling
ORCID
Venue
Aging
Publisher
Impact Journals, LLC
Published
2020-06-08
Volume
12
Issue
12
Pages
12222-12233
ISSN
1945-4589 (ISSN-L)
DOI
10.18632/aging.103405
PMC
PMC7343499
OpenAlex
W3033784070
Cited by
55
References
9
Citations by year
2026: 3 · 2025: 2 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 14 · 2020: 9
FWCI
10.05
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
  • Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
  • Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion, cc-by)
Funders
  • Medical Research Council (MR/M008924/1, MC_PC_17228)
  • National Institute on Aging (R21AG060018)
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 ε4, aging phenotypes, longevity, coronary artery disease, hypertension, lipid biomarkers, LDL cholesterol, triglycerides, renal function, frailty, anti-aging interventions, genetic variants
MeSH terms
Aged, Aging, Alleles, Apolipoproteins E, Female, Follow-Up Studies, United Kingdom, Humans, Male, Middle Aged, Morbidity, Mortality, Phenotype, Polymorphism, Genetic, Biomarkers, Biological Specimen Banks

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