Rare and common variants in the Apolipoprotein E gene in healthy oldest old.

Authors: Tindale LC; Leach S; Ushey K; Daley D; Brooks-Wilson AR

Abstract: Apolipoprotein E (APOE) alleles are associated with longevity in genome-wide scans, with epsilon4 correlated with shorter life, and epsilon2 with longer life, than epsilon3. We hypothesized that rare APOE variants with large individual effects might also contribute to long-term good health. The APOE exons and promoter were resequenced in DNA samples from 376 healthy oldest old aged >/= 85 yrs with no self-reported history of cancer, cardiovascular disease, diabetes, major pulmonary disease or Alzheimer disease ("Super-Seniors") and 376 population-based controls aged 41-54. Forty variants were observed: 32 were rare (minor allele frequency <2%); 9 were nonsynonymous. Controls were more likely to have an epsilon4 allele (Pearson chi(2) = 6.61, p = 0.04). Among the Super-Seniors, APOE allele status was not associated with body mass index or Mini Mental State Examination score. There was no excess of rare APOE variants in healthy oldest old compared with midlife controls, or vice-versa; however, this does not rule out an effect of some variants on ApoE function. Our findings were consistent with epsilon4 being a risk factor for early mortality.

Journal: Neurobiology of aging
Volume: 35
Issue: 3
Pages: 727.e1-3
Date: Oct. 16, 2013
PMID: 24126160
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Tindale LC, Leach S, Ushey K, Daley D, Brooks-Wilson AR (2014) Rare and common variants in the Apolipoprotein E gene in healthy oldest old. Neurobiology of aging 35: 727.e1-3.

Longevity Variant Associations (p-value):
  • e4 (0.04)

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