Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 8;12(12):12222-12233.
doi: 10.18632/aging.103405. Epub 2020 Jun 8.

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

Chia-Ling Kuo  1   2   3 , Luke C Pilling  3   4 , Janice L Atkins  4 , George A Kuchel  3 , David Melzer  3   4
Affiliations

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

Chia-Ling Kuo et al. Aging (Albany NY). .

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.

Keywords: coronary artery disease; e2e2; e2e3; hypertension; phenome-wide association study.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST: No conflicts of interest to disclose

Figures

Figure 1
Figure 1
Significant associations between e2e2 or e2e3 and biomarkers at the Bonferroni-corrected level of 5% (*p<0.05/106).
Figure 2
Figure 2
Significant associations between e2e2 or e2e3 and hematological measures at the Bonferroni-corrected level of 5% (*p<0.05/106).
Figure 3
Figure 3
Associations between e2 (e2e2 or e2e3) and primary disease outcomes. Note: Traits labelled with an asterisk if significant at the Bonferroni-corrected level of 5% (*p<0.05/106).
Figure 4
Figure 4
Associations between e2e2 or e2e3 and physical measures, cognitive function, and a 49-item frailty (*p<0.05/106).
Figure 5
Figure 5
Associations between e2e2 or e2e3 and parent, chronic pain, and physical measures (*p<0.05/106).
See this image and copyright information in PMC

References

    1. Suri S, Heise V, Trachtenberg AJ, Mackay CE. The forgotten APOE allele: a review of the evidence and suggested mechanisms for the protective effect of APOE ɛ2. Neurosci Biobehav Rev. 2013; 37:2878–86. 10.1016/j.neubiorev.2013.10.010 - DOI - PubMed
    1. Tudorache IF, Trusca VG, Gafencu AV. Apolipoprotein E - a multifunctional protein with implications in various pathologies as a result of its structural features. Comput Struct Biotechnol J. 2017; 15:359–65. 10.1016/j.csbj.2017.05.003 - DOI - PMC - PubMed
    1. Belloy ME, Napolioni V, Greicius MD. A quarter century of APOE and alzheimer’s disease: progress to date and the path forward. Neuron. 2019; 101:820–38. 10.1016/j.neuron.2019.01.056 - DOI - PMC - PubMed
    1. Eichner JE, Dunn ST, Perveen G, Thompson DM, Stewart KE, Stroehla BC. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol. 2002; 155:487–95. 10.1093/aje/155.6.487 - DOI - PubMed
    1. Huebbe P, Rimbach G. Evolution of human apolipoprotein E (APOE) isoforms: gene structure, protein function and interaction with dietary factors. Ageing Res Rev. 2017; 37:146–61. 10.1016/j.arr.2017.06.002 - DOI - PubMed

Publication types