Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.
FASEB J. 2011 Sep;25(9):3262-70. doi: 10.1096/fj.11-180935. Epub 2011 Jun 9.
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.
载脂蛋白 E (APOE) 的等位基因 ε4 是脂质代谢的关键调节因子，它是心血管疾病和阿尔茨海默病的风险因素。尽管它有不良影响，但该等位基因很常见，并且表现出非随机的全球分布，这被认为是进化适应的结果。一种假设提出，APOE ε4 等位基因可以预防维生素 D 缺乏症。在这里，我们首次提出了实验和流行病学证据，证明 APOE ε4 等位基因确实与更高的血清维生素 D [25(OH)D]水平相关。在 APOE4 靶向替换小鼠中，与 APOE2 和 APOE3 小鼠相比，25(OH)D 水平显著升高（70.9 与 41.8 和 27.8 nM，P<0.05）。此外，多元调整模型显示，APOE ε4 等位基因与一小部分人类受试者（n=93；P=0.072）和一般人群样本（n=699；P=0.003）中的 25(OH)D 水平呈正相关。这一新颖的联系表明 ε4 是维生素 D 状态的调节剂。虽然这一结果与进化方面一致，但与慢性疾病（尤其是心血管疾病）似乎存在矛盾。现在需要进行大规模的前瞻性队列研究，以研究这一发现对慢性疾病风险的潜在影响。
