title: APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans.
abstract: The allele ε4 of apolipoprotein E (APOE), which is a key regulator of lipid metabolism, represents a risk factor for cardiovascular diseases and Alzheimer's disease. Despite its adverse effects, the allele is common and shows a nonrandom global distribution that is thought to be the result of evolutionary adaptation. One hypothesis proposes that the APOE ε4 allele protects against vitamin D deficiency. Here we present, for the first time, experimental and epidemiological evidence that the APOE ε4 allele is indeed associated with higher serum vitamin D [25(OH)D] levels. In APOE4 targeted replacement mice, significantly higher 25(OH)D levels were found compared with those in APOE2 and APOE3 mice (70.9 vs. 41.8 and 27.8 nM, P<0.05). Furthermore, multivariate adjusted models show a positive association of the APOE ε4 allele with 25(OH)D levels in a small collective of human subjects (n=93; P=0.072) and a general population sample (n=699; P=0.003). The novel link suggests ε4 as a modulator of vitamin D status. Although this result agrees well with evolutionary aspects, it appears contradictory with regard to chronic diseases, especially cardiovascular disease. Large prospective cohort studies are now needed to investigate the potential implications of this finding for chronic disease risks.
authors.affiliation: Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Huebbe
authors.forename: Almut
authors.initials: A
authors.lastname: Nebel
authors.forename: Sabine
authors.initials: S
authors.lastname: Siegert
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moehring
authors.forename: Christine
authors.initials: C
authors.lastname: Boesch-Saadatmandi
authors.forename: Erika
authors.initials: E
authors.lastname: Most
authors.forename: Josef
authors.initials: J
authors.lastname: Pallauf
authors.forename: Sarah
authors.initials: S
authors.lastname: Egert
authors.forename: Manfred James
authors.initials: MJ
authors.lastname: Müller
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Ute
authors.initials: U
authors.lastname: Nöthlings
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D014807:Vitamin D / Q000097:blood*
chemical_list: D053327:Apolipoprotein E4; D014807:Vitamin D; D002118:Calcium