TY - JOUR
T1 - ApoE gene and exceptional longevity
T2 - Insights from three independent cohorts
AU - Garatachea, Nuria
AU - Emanuele, Enzo
AU - Calero, Miguel
AU - Fuku, Noriyuki
AU - Arai, Yasumichi
AU - Abe, Yukiko
AU - Murakami, Haruka
AU - Miyachi, Motohiko
AU - Yvert, Thomas
AU - Verde, Zoraida
AU - Zea, Ma Ascensión
AU - Venturini, Letizia
AU - Santiago, Catalina
AU - Santos-Lozano, Alejandro
AU - Rodríguez-Romo, Gabriel
AU - Ricevuti, Giovanni
AU - Hirose, Nobuyoshi
AU - Rábano, Alberto
AU - Lucia, Alejandro
N1 - Funding Information:
This study was funded by the Fondo de Investigaciones Sanitarias (FIS, ref. # PI12/00914 and FIS # PI12/00045 ) and Fundación Reina Sofía .
PY - 2014/5
Y1 - 2014/5
N2 - 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, 100-111. years) and healthy controls (n=1039, 20-85. years) from Spain; disease-free cases (centenarians; n=79, 100-104. years) and healthy controls (n=597, age 27-81. years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1. + major disease condition; n=729, 100-116. years) and healthy controls (n=498, 23-59. years) 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.
AB - 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, 100-111. years) and healthy controls (n=1039, 20-85. years) from Spain; disease-free cases (centenarians; n=79, 100-104. years) and healthy controls (n=597, age 27-81. years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1. + major disease condition; n=729, 100-116. years) and healthy controls (n=498, 23-59. years) 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.
KW - ApoE
KW - Case-control study
KW - Centenarians
KW - Genetics
KW - Longevity
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U2 - 10.1016/j.exger.2014.02.004
DO - 10.1016/j.exger.2014.02.004
M3 - Article
C2 - 24534555
AN - SCOPUS:84894652561
VL - 53
SP - 16
EP - 23
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
ER -