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

Authors: Garatachea N; Emanuele E; Calero M; Fuku N; Arai Y; Abe Y; Murakami H; Miyachi M; Yvert T; Verde Z; Zea MA; Venturini L; Santiago C; Santos-Lozano A; Rodríguez-Romo G; Ricevuti G; Hirose N; Rábano A; Lucia A

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 epsilon4-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 epsilon2-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 epsilon4-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 epsilon2-allele might favor EL, at least in the Italian and Japanese cohorts.

Journal: Experimental gerontology
Volume: 53
Pages: 16-23
Date: Feb. 19, 2014
PMID: 24534555
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Garatachea N, Emanuele E, Calero M, Fuku N, Arai Y, Abe Y, Murakami H, Miyachi M, Yvert T, Verde Z, Zea MA, Venturini L, Santiago C, Santos-Lozano A, Rodríguez-Romo G, Ricevuti G, Hirose N, Rábano A, Lucia A (2014) ApoE gene and exceptional longevity: Insights from three independent cohorts. Experimental gerontology 53: 16-23.

Longevity Variant Associations (p-value):
  • e4 (0.03)
  • e4 (0.05)
  • e4 (0.001)

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