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Exp Gerontol. 2014 May;53:16-23. doi: 10.1016/j.exger.2014.02.004. Epub 2014 Feb 15.

ApoE gene and exceptional longevity: Insights from three independent cohorts.

Author information

1
Faculty of Health and Sport Science, University of Zaragoza, Ronda Misericordia 5, 22001 Huesca, Spain; Hospital Universitario 12 de Octubre, Research Institute (i+12), Avda. de Córdoba s/n, 28041 Madrid, Spain. Electronic address: nuria.garatachea@unizar.es.
2
Department of Health Sciences, University of Pavia, Via Bassi, 21, I-27100 Pavia, Italy.
3
Fundación CIEN, Fundación Reina Sofía, Instituto de Salud Carlos III, Calle Valderrebollo 5, 28031 Madrid, Spain; UFIEC, Fundación CIEN-Fundación Reina Sofía, and CIBERNED - Instituto de Salud Carlos III, Madrid, Spain.
4
Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
5
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
6
Department of Health Promotion and Exercise, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, 162-8636 Tokyo, Japan.
7
European University of Madrid, Villaviciosa de Odón, 28670 Madrid, Spain.
8
Fundación CIEN, Fundación Reina Sofía, Instituto de Salud Carlos III, Calle Valderrebollo 5, 28031 Madrid, Spain.
9
Department of Biomedical Sciences, University of León, Campus de Vegazana s/n, 24071 León, Spain; Hospital Universitario 12 de Octubre, Research Institute (i+12), Avda. de Córdoba s/n, 28041 Madrid, Spain.
10
INEF, Universidad Politécnica, c/ Martín Fierro s/n, 28040 Madrid, Spain.
11
European University of Madrid, Villaviciosa de Odón, 28670 Madrid, Spain; Hospital Universitario 12 de Octubre, Research Institute (i+12), Avda. de Córdoba s/n, 28041 Madrid, Spain.

Abstract

The ApoE gene is associated with the risk of Alzheimer or cardiovascular disease but its influence on exceptional longevity (EL) is uncertain. Our primary purpose was to determine, using a case-control design, if the ApoE gene is associated with EL. We compared ApoE allele/genotype frequencies among the following cohorts: cases (centenarians, most with 1+ major disease condition; n=163, 100-111years) and healthy controls (n=1039, 20-85years) from Spain; disease-free cases (centenarians; n=79, 100-104years) and healthy controls (n=597, age 27-81years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1+ major disease condition; n=729, 100-116years) and healthy controls (n=498, 23-59years) from Japan. Our main findings were twofold. First, the ε4-allele was negatively associated with EL in the three cohorts, with the following odds ratio (OR) values (adjusted by sex) having been found: 0.55 (95% confidence interval (CI): 0.33, 0.94), P=0.030 (Spain); 0.41 (95%CI: 0.18, 0.99), P=0.05 (Italy); and 0.35 (95%CI: 0.26, 0.57), P<0.001 (Japan). Second, although no association was found in the Spanish cohort (OR=1.42 (95%CI: 0.89, 2.26), P=0.145), the ε2-allele was positively associated with EL in the Italian (OR=2.14 (95%CI: 1.18, 3.45), P=0.01) and Japanese subjects (OR=1.81 (95%CI: 1.25, 2.63), P=0.002). Notwithstanding the limitations of case-control designs, our data suggest that the ApoE might be a candidate to influence EL. The ε4-allele appears to decrease the likelihood of reaching EL among individuals of different ethnic/geographic origins. An additional, novel finding of our study was that the ε2-allele might favor EL, at least in the Italian and Japanese cohorts.

KEYWORDS:

ApoE; Case-control study; Centenarians; Genetics; Longevity

PMID:
24534555
DOI:
10.1016/j.exger.2014.02.004
[Indexed for MEDLINE]

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