title: ApoE gene and exceptional longevity: Insights from three independent cohorts.
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.
authors.affiliation: 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.
authors.forename: Nuria
authors.initials: N
authors.lastname: Garatachea
authors.affiliation: Department of Health Sciences, University of Pavia, Via Bassi, 21, I-27100 Pavia, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.affiliation: 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.
authors.forename: Miguel
authors.initials: M
authors.lastname: Calero
authors.affiliation: Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Fuku
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Health Promotion and Exercise, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, 162-8636 Tokyo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Department of Health Promotion and Exercise, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, 162-8636 Tokyo, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Miyachi
authors.affiliation: European University of Madrid, Villaviciosa de Odón, 28670 Madrid, Spain.
authors.forename: Thomas
authors.initials: T
authors.lastname: Yvert
authors.affiliation: European University of Madrid, Villaviciosa de Odón, 28670 Madrid, Spain.
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Verde
authors.affiliation: Fundación CIEN, Fundación Reina Sofía, Instituto de Salud Carlos III, Calle Valderrebollo 5, 28031 Madrid, Spain.
authors.forename: Ma Ascensión
authors.initials: MA
authors.lastname: Zea
authors.affiliation: Department of Health Sciences, University of Pavia, Via Bassi, 21, I-27100 Pavia, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Venturini
authors.affiliation: European University of Madrid, Villaviciosa de Odón, 28670 Madrid, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.affiliation: 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.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Santos-Lozano
authors.affiliation: INEF, Universidad Politécnica, c/ Martín Fierro s/n, 28040 Madrid, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rodríguez-Romo
authors.affiliation: Department of Health Sciences, University of Pavia, Via Bassi, 21, I-27100 Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ricevuti
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
authors.affiliation: Fundación CIEN, Fundación Reina Sofía, Instituto de Salud Carlos III, Calle Valderrebollo 5, 28031 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rábano
authors.affiliation: 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.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E
keywords: ApoE; Case-control study; Centenarians; Genetics; Longevity