Sex Differences in the Association of Apolipoprotein E and Angiotensin-Converting Enzyme Gene Polymorphisms With Healthy Aging and Longevity: A Population-Based Study From Southern Italy

Seripa, Davide; Franceschi, Marilisa; Matera, Maria G.; Panza, Francesco; Kehoe, Patrick Gavin; Gravina, Carolina; Orsitto, Giuseppe; Solfrizzi, Vincenzo; Minno, Giovanni Di; Dallapiccola, Bruno; Pilotto, Alberto

doi:10.1093/gerona/61.9.918

Cited by 76 publications

(57 citation statements)

References 31 publications

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“…The ε4-allele frequency in our Spanish (10%) and Italian (8%) young controls was relatively higher than that previously reported by Lewis and Brunner (2004) in Southern Europe. Whereas, the ApoE ε4-allele frequency in Spanish and Italian centenarians was 4.9 and 3.2% respectively, which is within the range of previously published frequencies (1-10%) for European centenarians (Blanche et al, 2001;Capurso et al, 2004;Castro et al, 1999;Gerdes et al, 2000;Louhija et al, 1994;Maruszak et al, 2012;Panza et al, 1999;Panza et al, 2003;Schachter et al, 1994;Seripa et al, 2006). On the other hand, allele frequencies in the Japanese centenarians studied here (ε2 = 7.3%; ε3 = 88.1%; ε4 = 4.6%) are comparable to those previously reported in centenarians of the same country, e.g., ε2 = 4.5%; ε3 = 90.9%; ε4 = 4.5% (Asada et al 1996).…”

Section: Discussionsupporting

confidence: 85%

“…The explanation for our novel finding, i.e., that the ε2-allele could benefit EL in the Italian and Japanese population, and specifically favor healthy attainment of EL in the Italian cohort, is less apparent and warrants further research. The ApoE ε2-allele has previously been reported to be more frequent in centenarians (Blanche et al, 2001;Louhija et al, 1994;Schachter et al, 1994;Seripa et al, 2006) than in younger people, but others found no differences (Asada et al, 1996;Capurso et al, 2004;Feng et al, 2011;Louhija et al, 2001;Panza et al, 1999). A meta-analysis considering only studies of centenarians published before 2004 gave a point estimate of 1.50 (95%CI, 1.27-1.78) for ε2-allele frequency in centenarians vs. younger controls (Lewis and Brunner, 2004).…”

Section: Discussionmentioning

confidence: 96%

“…However, others found no association of this variant with EL in Japanese (Asada et al, 1996), Finnish (Louhija et al, 2001) or Southern-Italian centenarians (Capurso et al, 2004). Concurrently, the ApoE ε2-allele has been reported to be more frequent in centenarians (Blanche et al, 2001;Louhija et al, 1994;Schachter et al, 1994;Seripa et al, 2006) than in younger people, but others found no differences (Asada et al, 1996;Feng et al, 2011;Louhija et al, 2001;Panza et al, 1999). A meta-analysis reported a point estimate of 1.50 [95% confidence intervals (CI): 1.27, 1.78] and 0.49 (95%CI: 0.41, 0.58) for the frequency of ε2 and ε4-alleles, respectively, in centenarians vs. younger controls, but only studies published before 2004 were included in the review (Lewis and Brunner, 2004).…”

Section: Introductionmentioning

confidence: 99%

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ApoE gene and exceptional longevity: Insights from three independent cohorts

Garatachea

Emanuele

Calero

et al. 2014

Experimental Gerontology

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. 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 b 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.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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ApoE gene and exceptional longevity: Insights from three independent cohorts

Garatachea

Emanuele

Calero

et al. 2014

Experimental Gerontology

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“…However, two loci that are repeatedly found by GWAS of aging are APOE (Deelen et al, 2011; Ewbank, 2007; Gerdes, Jeune, Ranberg, Nybo, & Vaupel, 2000) and FOXO3A (Anselmi et al, 2009; Flachsbart et al, 2009; Li et al, 2009; Pawlikowska et al, 2009; Willcox et al, 2008). Similar to AD, APOE ε2 is found to be enriched in elderly and centenarians compared to younger individuals (Seripa et al, 2006). Elder APOE ε2 carriers were found to have reduced accumulation of amyloid pathology via multimodal neuroimaging (Grothe et al, 2017).…”

Section: Molecular Links Between Aging and Admentioning

confidence: 99%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.

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“…Nuestros resultados son similares a aquellos trabajos que mostraron una relación entre la longevidad y el genotipo de ACE (34)(35)(36), siendo el alelo D favorable en cuanto a longevidad. En su estudio, Kritchevsky y cols.…”

Section: Discussionunclassified

Obesidad Sarcopénica en Mujeres Mayores: Influencia Del Polimorfismo I/D De Ace

et al. 2017

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Palabras clave:Personas mayores. Polimorfismo genético. Sarcopenia. Obesidad. Actividad física. ResumenIntroducción: la obesidad sarcopénica (OS) es un término que relaciona el aumento de la masa grasa con la disminución de la masa muscular y que afecta a un importante porcentaje de población mayor. La falta de ejercicio regular y factores genéticos relacionados con el envejecimiento y la condición física podrían influir en su aparición. Objetivo: determinar si las mujeres mayores de 60 años que practican de forma continuada ejercicio físico presentan diferencias en la obesidad sarcopénica en función del polimorfismo I/D del gen de la enzima convertidora de angiotensina (ACE). Métodos: estudio transversal de 300 mujeres mayores que realizaban ejercicio físico al menos dos veces a la semana en los últimos dos años. Se tomaron datos de medidas antropométricas, cuestionario de comportamiento actividad-sedentarismo, evaluación de la obesidad sarcopénica (a través de la determinación del porcentaje de masa grasa y masa muscular total mediante impedancia eléctrica y la agrupación de los quintiles de estos valores en cuatro grupos), evaluación de la condición física y genotipado del gen ACE mediante extracción de ADN de mucosa oral. Resultados: se encontraron diferencias significativas en la obesidad sarcopénica en función del genotipo I/D de ACE. Las mujeres del grupo ACE DD presentaron menor riesgo de padecer obesidad sarcopénica que aquellas con genotipo ACE II y ACE ID (valores OS: 2.18 genotipo ACE DD frente a 2.48 genotipo ACE II + ACE ID; p < 0,05). Conclusiones: las mujeres mayores de 60 años con genotipo ACE DD que practican ejercicio regularmente presentan menor riesgo de padecer obesidad sarcopénica. Key words:Elderly. Genetic polymorphism. Sarcopenia. Obesity. Exercise. AbstractIntroduction: Sarcopenic obesity (SO) is a term that refers to an increase of fat mass together with a decrease of muscle mass, which is suffered by a high percentage of elderly population. Physical activity seems to be a good strategy to prevent it getting worse. However, genetic factors related to the aging process and to elderly's physical fitness could have an influence on it. Aim: To determine if elderly women > 60 who practice physical activity regularly had differences in sarcopenic obesity according to the I/D polymorphism from the ACE (angiotensin converter enzyme) gen. Methods: Cross-sectional study of 300 elderly women who have practiced physical exercise at least twice a week for the past two years. Anthropometric data, physical activity and sedentary behaviour questionnaire, sarcopenic obesity (determining the percentage of fat mass and total muscle mass by electrical impedance and grouping the quintiles of these values into four groups) and physical fitness assessment, as well as ACE gen genotype measured by oral mucosa sample, were evaluated. Results: There were significant differences (p < 0.05) in sarcopenic obesity according to ACE I/D genotype (SO values: 2.18 ACE DD vs 2.48 ACE II + ACE ID). Conclusions: Women who...

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Sex Differences in the Association of Apolipoprotein E and Angiotensin-Converting Enzyme Gene Polymorphisms With Healthy Aging and Longevity: A Population-Based Study From Southern Italy

Cited by 76 publications

References 31 publications

ApoE gene and exceptional longevity: Insights from three independent cohorts

ApoE gene and exceptional longevity: Insights from three independent cohorts

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

Obesidad Sarcopénica en Mujeres Mayores: Influencia Del Polimorfismo I/D De Ace

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