Health-protective and adverse effects of the apolipoprotein E ε2 allele in older men

OBJECTIVES: To reexamine a health-protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOE epsilon 2-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 epsilon 2-containing genotypes. RESULTS: The epsilon 2/3 genotype is a major contributor to adverse associations between the epsilon 2 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 epsilon 2-containing genotypes and disability. Protective effects of the epsilon 2/3 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 epsilon 2-containing genotypes and IADL are found in women. CONCLUSION: The epsilon 2 allele can play a dual role in men, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that epsilon 2-containing genotypes can be unfavorable factors for the health and well-being of aging men.