Is APOE $\boldsymbol{\varepsilon}$ 3 a favourable factor for the longevity: an association study in Chinese population

Feng, Jie; Li, Xiang; Wu, Gang; Qi, Keyan; Sun, Liang; Huang, Zezhi; Zheng, Chengchao; Lv, Zhen; Yang, Ze

doi:10.1007/s12041-011-0075-9

Cited by 21 publications

(18 citation statements)

References 15 publications

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“…This view is in line with the 'heterogeneity hypothesis', according to which mortality of individuals carrying the 'frail' genotype (e.g., one or more ε4-alleles) in a population will approach that of non-carriers with advancing age because of a selection pressure on carriers; that is, surviving carriers might possess other factors compensating for the 'frail' genotype, and thus heterogeneity becomes a more important factor at old ages than carriage of a given risk-allele . However, our results seem to be in support of previous data on Scandinavian twins showing an increasing mortality risk associated with the ApoE ε4-allele with advancing age (Hjelmborg et al, 2006) or of those showing lower frequency of this allele in centenarians compared with younger controls of French (Blanche et al, 2001;Schachter et al, 1994), Finnish (Louhija et al, 1994), Southern Italian (Panza et al, 1999) or Chinese origin (Feng et al, 2011). Thus, our data seem in agreement with an another hypothesis, the so-called 'multifactorial threshold model', according to which many single factors (e.g., carriage of a frail genotype such as one or more ε4-alleles) each with small yet significant effect add up and contribute to a disorder/condition (or death) to happen with age (Jacobsen et al, 2010).…”

Section: Discussionsupporting

confidence: 91%

“…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%

“…The majority of reports indicate a lower frequency of the ApoE ε4-allele in centenarians compared with younger controls, i.e., in French (Blanche et al, 2001;Schachter et al, 1994), Finnish (Louhija et al, 1994), Southern Italian (Panza et al, 1999), or Chinese cohorts (Feng et al, 2011). 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).…”

Section: Introductionmentioning

confidence: 99%

“…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: 91%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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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“…Presenta tres alelos principales: ε2, ε3 y ε4, que se transmiten en forma codominante, codifican para tres diferentes isoformas de proteínas llamadas apolipoproteínas E2, E3 y E4, y se diferencian por un cambio de nucleótido C/T en el exón 4 en las posiciones 112 y 158 de la secuencia aminoacídica, donde hay un cambio de arginina o cisteína (4)(5)(6). La isoforma APOE2 presenta residuos de cisteína (TGC) en la posición 112 y 158; la APOE3 presenta cisteína (TGC) en la posición 112 y arginina (CGC) en la posición 158, en tanto que la APOE4 presenta arginina (CGC) en las dos posiciones y origina, a su vez, seis genotipos: ε2/ε2, ε3/ ε3, ε2/ε3, ε3/ε4, ε2/ε4 y ε4/ε4 (7).…”

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Análisis del polimorfismo del gen APOE en la población de Barranquilla, Colombia

et al. 2015

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Introducción. La variabilidad genética del polimorfismo del gen APOE se considera un importante factor asociado a la predisposición a las enfermedades que afectan el metabolismo lipídico, a las enfermedades coronarias y a la enfermedad de Alzheimer, entre otras. En este sentido, es útil conocer este factor de riesgo en diferentes poblaciones y grupos étnicos. Objetivos. Analizar el polimorfismo del gen APOE y determinar las frecuencias alélicas y genotípicas de una muestra representativa de la población de Barranquilla, Colombia. Materiales y métodos. Se hizo en Barranquilla un estudio descriptivo y comparativo de 227 individuos no relacionados. Resultados. El alelo ε3 se presentó con mayor frecuencia (85 %), seguido del alelo ε4 (13 %) y, con menor frecuencia, el alelo ε2 (1,8 %). Los genotipos observados fueron los siguientes: ε3/ε3 en 71,8 %, ε3/ε4 en 24,2 %, ε2/ε3 en 2,2 %, ε2/ε4 en 1,3 % y ε4/ε4 en 0,4 %. El genotipo ε2/ε2 no se encontró en este estudio. La muestra representativa de la población estaba en equilibrio de Hardy-Weinberg. Conclusiones. Las frecuencias alélicas ε3 y el genotipo ε3/ε3 encontrados en la población estudiada, fueron similares a lo informado por la literatura científica en países como Brasil, México y Colombia, y en algunos grupos étnicos amerindios colombianos. No se encontró el genotipo ε2/ε2, resultado que coincide con otras poblaciones estudiadas a nivel mundial. La frecuencia del alelo ε4 y sus genotipos asociados en esta población, podría estar relacionada con la presencia de enfermedades como la hipercolesterolemia, el infarto de miocardio y la enfermedad de Alzheimer.Palabras clave: apolipoproteínas E, polimorfismo genético, población, alelos, Colombia. doi: http://dx.doi.org/10.7705/biomedica.v36i1.2612 APOE gene polymorphism analysis in Barranquilla, ColombiaIntroduction: The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool. Objective: To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia. Materials and methods:We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia Results: The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium. Conclusion: The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in oth...

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Detecting Polymorphisms in Human Longevity Studies: HLA Typing and SNP Genotyping by Amplicon Sequencing

Vargas‐Alarcón

Flores-Domı́nguez

2013

Methods in Molecular Biology

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Life expectancy has always been associated to several determinants, such as environmental and genetic factors. Studies have related human lifespan as being 25-32 % due to genetic polymorphisms between individuals associated to longevity and aging. Nonetheless, no single gene will convey a phenotype like longevity. Aging is a process that occurs from changes in various levels of the cell, from genes to functions. Longevity is the ability to cope and repair the damage that results from these changes. It has been described as the result of an optimal performance of immune system and as an overexpression of anti-inflammatory sequence variants of immune/inflammatory genes.Longevity gene candidates can be separated into the following categories: inflammatory and immune-related, stress response elements, mediators of glucose and lipid metabolism, DNA repair components and cellular proliferation, and DNA haplogroups.Studies have related lifespan with Common Single-Nucleotide Polymorphisms (SNPs); polygenic effects can explain an important part of how genetics influence it. In this chapter we describe how to sequence Class I HLA allele polymorphism, as well as SNP sequencing, two methodologies most frequently used in polymorphism detection.

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Is APOE $\boldsymbol{\varepsilon}$ 3 a favourable factor for the longevity: an association study in Chinese population

Cited by 21 publications

References 15 publications

ApoE gene and exceptional longevity: Insights from three independent cohorts

ApoE gene and exceptional longevity: Insights from three independent cohorts

Análisis del polimorfismo del gen APOE en la población de Barranquilla, Colombia

Detecting Polymorphisms in Human Longevity Studies: HLA Typing and SNP Genotyping by Amplicon Sequencing

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