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Genes (Basel). 2019 Mar 15;10(3). pii: E222. doi: 10.3390/genes10030222.

The Genetic Variability of APOE in Different Human Populations and Its Implications for Longevity.

Author information

1
Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, Italy. paolo.abondio2@unibo.it.
2
Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, Italy. marco.sazzini2@unibo.it.
3
Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy. paolo.garagnani2@unibo.it.
4
Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, Italy. alessio.boattini2@unibo.it.
5
Department of Biomedical, Clinical and Experimental Sciences "Mario Serio", University of Florence, 50134 Florence, Italy. daniela.monti@unifi.it.
6
IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy. claudio.franceschi@unibo.it.
7
Department of Cultural Heritage (DBC), University of Bologna, Ravenna Campus, 48121 Ravenna, Italy. donata.luiselli@unibo.it.
8
Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, Italy. cristina.giuliani2@unibo.it.
9
School of Anthropology and Museum Ethnography, University of Oxford, OX2 6PE Oxford, UK. cristina.giuliani2@unibo.it.

Abstract

Human longevity is a complex phenotype resulting from the combinations of context-dependent gene-environment interactions that require analysis as a dynamic process in a cohesive ecological and evolutionary framework. Genome-wide association (GWAS) and whole-genome sequencing (WGS) studies on centenarians pointed toward the inclusion of the apolipoprotein E (APOE) polymorphisms ε2 and ε4, as implicated in the attainment of extreme longevity, which refers to their effect in age-related Alzheimer's disease (AD) and cardiovascular disease (CVD). In this case, the available literature on APOE and its involvement in longevity is described according to an anthropological and population genetics perspective. This aims to highlight the evolutionary history of this gene, how its participation in several biological pathways relates to human longevity, and which evolutionary dynamics may have shaped the distribution of APOE haplotypes across the globe. Its potential adaptive role will be described along with implications for the study of longevity in different human groups. This review also presents an updated overview of the worldwide distribution of APOE alleles based on modern day data from public databases and ancient DNA samples retrieved from literature in the attempt to understand the spatial and temporal frame in which present-day patterns of APOE variation evolved.

KEYWORDS:

APOE; apolipoprotein E; genomics; longevity; populations

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