Health-protective and adverse effects of the apolipoprotein E epsilon2 allele in older men.
OBJECTIVE
To reexamine a health-protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOE epsilon2-containing genotypes and impairments in instrumental activities of daily living (IADLs) in older (> or = 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.


METHODS
Retrospective cross-sectional study.


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


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


METHODS
Indicators of IADL impairments, five geriatric disorders, and epsilon2-containing genotypes.


RESULTS
The epsilon2/3 genotype is a major contributor to adverse associations between the epsilon2 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 epsilon2-containing genotypes and disability. Protective effects of the epsilon2/3 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 epsilon2-containing genotypes and IADL are found in women.


CONCLUSIONS
The epsilon2 allele can play a dual role in men, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that epsilon2-containing genotypes can be unfavorable factors for the health and well-being of aging men.
Kulminski
Alexander M
AM
Center for Population Health and Aging, Duke University, Trent Hall, Room 002, Trent Drive, Box 90408, Durham, NC 27708, USA. Alexander.Kulminski@duke.edu
Ukraintseva
Svetlana V
SV
Arbeev
Konstantin G
KG
Manton
Kenneth G
KG
Oshima
Junko
J
Martin
George M
GM
Il'yasova
Dora
D
Yashin
Anatoli I
AI
D000203:Activities of Daily Living; D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053329:Apolipoprotein E2 / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012737:Sex Factors
D053329:Apolipoprotein E2