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Research Paper|Volume 12, Issue 12|pp 12222—12233

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

Chia-Ling Kuo1,2,3, Luke C. Pilling3,4, Janice L. Atkins4, George A. Kuchel3, David Melzer3,4
  • 1Department of Public Health Sciences, University of Connecticut Health, Farmington, CT 06032, USA
  • 2Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06032, USA
  • 3Center on Aging, School of Medicine, University of Connecticut Health, Farmington, CT 06030, USA
  • 4College of Medicine and Health, University of Exeter, Exeter, Devon, UK
Received: February 10, 2020Accepted: May 25, 2020Published: June 8, 2020
https://doi.org/10.18632/aging.103405

Copyright © 2020 Kuo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.