• apolipoprotein E;
  • cardiovascular disease;
  • disability;
  • sex differences

OBJECTIVES: To reexamine a health-protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOEɛ2—containing genotypes and impairments in instrumental activities of daily living (IADLs) in older (≥65) men and women and to examine how diagnosed coronary heart disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration, and atherosclerosis may mediate these connections.

DESIGN: Retrospective cross-sectional study.

SETTING: The unique disability-focused data from a genetic subsample of the 1999 National Long Term Care Survey linked with Medicare service use files.

PARTICIPANTS: One thousand seven hundred thirty-three genotyped individuals interviewed regarding IADL disabilities.

MEASUREMENTS: Indicators of IADL impairments, five geriatric disorders, and ɛ2-containing genotypes.

RESULTS: The ɛ2/3 genotype is a major contributor to adverse associations between the ɛ2 allele and IADL disability in men (odds ratio (OR)=3.09, 95% confidence interval (CI)=1.53–6.26), although it provides significant protective effects for CHD (OR=0.55, 95% CI=0.33–0.92), whereas CHD is adversely associated with IADL disability (OR=2.18, 95% CI=1.28–3.72). Adjustment for five diseases does not significantly alter the adverse association between ɛ2-containing genotypes and disability. Protective effects of the ɛ2/3 genotype for CHD (OR=0.52, 95% CI=0.27–0.99) and deleterious effects for IADLs (OR=3.50, 95% CI=1.71–7.14) for men hold in multivariate models with both these factors included. No significant associations between the ɛ2-containing genotypes and IADL are found in women.

CONCLUSION: The ɛ2 allele can play a dual role in men, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that ɛ2-containing genotypes can be unfavorable factors for the health and well-being of aging men.