Evolution of human apolipoprotein E (APOE) isoforms: gene structure, protein function and interaction with dietary factors.

Evolution of human apolipoprotein E (APOE) isoforms: gene structure, protein function and interaction with dietary factors.
Ageing Res Rev. 2017 Jun 21;:
Authors: Huebbe P, Rimbach G
Abstract
Apolipoprotein E (APOE) is a member of the vertebrate protein family of exchangeable apolipoproteins that is characterized by amphipathic α-helices encoded by multiple nucleotide tandem repeats. Its equivalent in flying insects - apolipophorin-III - shares structural and functional commonalities with APOE, suggesting the possibility of an evolutionary relationship between the proteins. In contrast to all other known species, human APOE is functionally polymorphic and possesses three major allelic variants (ε4, ε3 and ε2). The present review examines the current knowledge on APOE gene structure, phylogeny and APOE protein topology as well as its human isoforms. The ε4 allele is associated with an increased age-related disease risk but is also the ancestral form. Despite increased mortality in the elderly, ε4 has not become extinct and is the second-most common allele worldwide after ε3. APOE ε4, moreover, shows a non-random geographical distribution, and similarly, the ε2 allele is not homogenously distributed among ethnic populations. This likely suggests the existence of selective forces that are driving the evolution of human APOE isoforms, which may include differential interactions with dietary factors. To that effect, micronutrient...

Source: Ageing Research Reviews - June 21, 2017 Category: Genetics & Stem Cells Authors: Huebbe P, Rimbach G Tags: Ageing Res Rev Source Type: research