APOEε4is 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.

An Intervention Study of Individual, apoE Genotype-Based Dietary and Physical-Activity Advice: Impact on Health Behavior

“…As mentioned in the literature review, some studies have shown a connection between apoE genotypes and vitamin D metabolism [15,31]. This fact could have been included in the messages, especially since a low vitamin D concentration in the serum is a factor predisposing to CVD [15].…”

“…Carriers of the apoE ԑ4 allele may even have a 42% higher risk for CVD than carriers of the apoE 3/3 genotype [14]. It is also known that a low vitamin D serum level is a risk factor for CVD [15]. The reported relation between apoE genotype and serum vitamin D content may be due to the better absorption of dietary fats among apoE ε4 carriers [15].…”

“…It is also known that a low vitamin D serum level is a risk factor for CVD [15]. The reported relation between apoE genotype and serum vitamin D content may be due to the better absorption of dietary fats among apoE ε4 carriers [15]. Several studies have shown that apoE ε4 carriers respond better to dietary changes (in fat quality) and exercise than apoE ε3 or ε2 carriers [12,16].…”

ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

“…An alternative (n-3) PUFA is Table 4. Effects of the apoE isoform on parameters of vitamin D and Ca status evident in apoE4 compared with apoE3 targeted gene replacement mice (46) Parameter Renal absorption of Ca from primary urine (Trpv6, S100g)…”

Apolipoprotein E polymorphism and functional disability in Brazilian elders: the Bambuí Health and Aging Study

“…Another potential explanation for the results found in the present study is the fact that the presence of the ε4 allele leads to greater intestinal absorption and renal reuptake of vitamin D 39 . It has been suggested that higher concentrations of this vitamin may promote physical performance 40,41 , decreasing the risk of mobility limitation 42 .…”