title: Rare and common variants in the Apolipoprotein E gene in healthy oldest old.
abstract: Apolipoprotein E (APOE) alleles are associated with longevity in genome-wide scans, with ε4 correlated with shorter life, and ε2 with longer life, than ε3. 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 ε4 allele (Pearson χ(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 ε4 being a risk factor for early mortality.
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Tindale
authors.forename: Stephen
authors.initials: S
authors.lastname: Leach
authors.forename: Kevin
authors.initials: K
authors.lastname: Ushey
authors.forename: Denise
authors.initials: D
authors.lastname: Daley
authors.forename: Angela R
authors.initials: AR
authors.lastname: Brooks-Wilson
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000483:Alleles; D053329:Apolipoprotein E2 / Q000235:genetics; D053318:Apolipoprotein E3 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E
keywords: APOE; Apolipoprotein E; Healthy aging; Longevity; Oldest old