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Related Experiment Videos

Apolipoprotein E genotype and mortality: findings from the Cache County Study.

Kathleen M Hayden1, Peter P Zandi, Constantine G Lyketsos

  • 1Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina.

Journal of the American Geriatrics Society
|June 7, 2005
PubMed
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The apolipoprotein E (apo E) epsilon4 genotype is linked to increased mortality risk in older adults. Alzheimer's disease partially explains this association, highlighting its role in early mortality.

Area of Science:

  • Genetics and Aging Research
  • Neurodegenerative Diseases
  • Cardiovascular Epidemiology

Background:

  • The apolipoprotein E (apo E) gene influences lipid metabolism and is implicated in Alzheimer's disease (AD) and cardiovascular disease (CVD).
  • The epsilon4 (ε4) allele of apo E is a known risk factor for late-onset AD.
  • The association between apo E genotypes and overall mortality, particularly considering the contributions of AD and CVD, requires further investigation.

Purpose of the Study:

  • To assess the relationship between apolipoprotein E (apo E) epsilon4 (ε4) genotype and mortality risk in an elderly population.
  • To determine the population attributable risk for mortality associated with the apo E ε4 allele.
  • To elucidate the relative contributions of cardiovascular disease (CVD) and Alzheimer's disease (AD) in mediating this mortality risk.

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Main Methods:

  • A population-based cohort study was conducted with community-dwelling permanent residents of Cache County, Utah, aged 65 and older.
  • Participants were genotyped for the apo E locus using DNA extracted from buccal swabs.
  • Mortality data were obtained from vital statistics reports, while AD diagnoses followed established criteria and CVD status was ascertained through interviews.

Main Results:

  • The apo E epsilon2/2 (ε2/2), epsilon3/4 (ε3/4), and epsilon4/4 (ε4/4) genotypes were associated with increased mortality risk compared to the epsilon3/3 (ε3/3) genotype, even after adjusting for demographic factors.
  • After adjusting for AD, the increased mortality risk associated with the ε3/4 and ε4/4 genotypes was reduced, suggesting a mediating role for AD.
  • The population attributable risk for mortality for combined ε3/4 and ε4/4 genotypes was estimated at 9.6%.

Conclusions:

  • The apo E ε2/2, ε3/4, and ε4/4 genotypes are associated with elevated risks of early mortality.
  • Alzheimer's disease partially mediates the association between apo E ε3/4 and ε4/4 genotypes and mortality.
  • These findings underscore the significant impact of specific apo E genotypes on mortality, with AD playing a crucial mediating role.