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Age and Ageing Advance Access published online on February 4, 2008
Age and Ageing, doi:10.1093/ageing/afn003
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Copyright © The Author 2008. Published by Oxford University Press on behalf of the British Geriatrics Society.

Association between APOE {varepsilon}2/{varepsilon}3/{varepsilon}4 polymorphism and disability severity in a national long-term care survey sample

Alexander Kulminski1,, Svetlana V. Ukraintseva1, Konstantin G. Arbeev1, Kenneth G. Manton3, Junko Oshima2, George M. Martin2 and Anatoli I. Yashin1

1 Center for Population Health and Aging, Duke University Population Research Institute and Department of Sociology, Duke University, Trent Hall, Room 002, Durham, NC 27708, USA
2 Department of Pathology, University of Washington, HSB K-543, 1959 NE Pacific Ave, Seattle, WA 98195-7470, USA
3 Art and Sciences, Duke University, Trent Hall, Room 012, Durham, NC 27708, USA

Address correspondence to: Alexander Kulminski. Tel: 919-684-4962; Fax: 919-684-3861. Email: Alexander.Kulminski{at}duke.edu

Background: early studies reported controversial findings on association of apolipoprotein E (APOE) polymorphism with disability.

Objective: to analyse sex-specific associations of APOE genotypes with impairments in (instrumental) activities of daily living [(I)ADL] and mortality.

Design: population-based 1999 National Long Term Care Survey (NLTCS) of the US older (65+) individuals.

Participants: genetic data are available for 1,805 individuals.

Methods: each of six genotypes of three common alleles of the APOE locus ({varepsilon}2, {varepsilon}3 and {varepsilon}4) was tested on the association with a disability index or mortality.

Results: APOE {varepsilon}3/{varepsilon}3 genotype significantly decreases odds ratio (OR) for IADL disability in males [OR = 0.48; 95% Confidence Interval (CI) 0.31–0.76] while it exhibits no association in females. The OR for ADL disability is 0.19 (CI 0.04–0.99) for {varepsilon}4/{varepsilon}4 female carriers. The {varepsilon}2/{varepsilon}3 genotype increases the chances of IADL disability for males (OR = 2.33; CI 1.28–4.25). No significant association between APOE polymorphism and mortality was found. A surprising observation was that {varepsilon}4/{varepsilon}4 female carriers have a 5.3 times lower chance of having ADL disability than non-{varepsilon}4/{varepsilon}4-carriers.

Conclusions: association of the APOE polymorphism with disability and lack of association with mortality support the view that APOE gene actions may be more significant as modulators of frailty than of longevity.

Keywords: apolipoprotein E, disability, sex differences, elderly

Received 15 February 2007; accepted in revised form 27 September 2007.


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