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APOE ε 4 is associated with higher vitamin D levels in targeted replacement mice and humans
Author(s) -
Huebbe Patricia,
Nebel Almut,
Siegert Sabine,
Moehring Jennifer,
BoeschSaadatmandi Christine,
Most Erika,
Pallauf Josef,
Egert Sarah,
Müller Manfred James,
Schreiber Stefan,
Nöthlings Ute,
Rimbach Gerald
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-180935
Subject(s) - apolipoprotein e , allele , vitamin d and neurology , apolipoprotein b , endocrinology , disease , medicine , population , risk factor , cohort , biology , physiology , genetics , cholesterol , gene , environmental health
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.—Huebbe, P., Nebel, A., Siegert, S., Moehring, J., Boesch‐Saadatmandi, C., Most, E., Pallauf, J., Egert, S., Müller, M. J., Schreiber, S., Nöthlings, U., Rimbach, G. APOE ε 4 is associated with higher vitamin D levels in targeted replacement mice and humans. FASEB J. 25, 3262‐3270 (2011). www.fasebj.org