• Nuria Garatachea, Enzo Emanuele, Miguel Calero, Noriyuki Fuku, Yasumichi Arai, Yukiko Abe, Haruka Murakami, Motohiko Miyachi, Thomas Yvert, Zoraida Verde, Ma Ascensión Zea, Letizia Venturini, Catalina Santiago, Alejandro Santos-Lozano, Gabriel Rodríguez-Romo, Giovanni Ricevuti, Nobuyoshi Hirose, Alberto Rábano, and Alejandro Lucia.
• 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.
• Exp. Gerontol. 2014 May 1;53:16-23.

AbstractThe 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.Copyright © 2014 Elsevier Inc. All rights reserved.

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