Implications of apolipoprotein E genotype on inflammation and vitamin E status

Abstract

In Western societies the apolipoprotein E4 (apoE4) genotype is associated with increased morbidity and mortality and represents a significant risk factor for cardiovascular and Alzheimer's disease. In a recent study we observed significantly lower tissue alpha-tocopherol (alpha-TOH) concentrations in apoE4 compared with apoE3 mice. Furthermore, genes encoding for proteins involved in peripheral alpha-TOH transport and degradation were affected by the apoE genotype. Thus, the apoE4 genotype may be associated with lower vitamin E retention in peripheral tissues. This is possibly related to an altered lipoprotein metabolism including increased alpha-TOH retention in LDL, a decreased expression of lipoprotein receptors and impaired cellular vitamin E delivery system, and a greater intracellular degradation of tocopherols in the apoE4 genotype. An increasing number of studies in cultured cells, transgenic mice and human volunteers indicate a more pro-inflammatory state associated with the apoE4 allele. In apoE4 macrophages there is an enhanced transactivation of the key redox sensitive transcription factor NF-kappaB accompanied by a higher production of pro-inflammatory molecules (tumor necrosis factor alpha, interleukin 1beta, macrophage inflammatory protein 1-alpha) and a lower production of anti-inflammatory interleukin 10, as compared with apoE3 macrophages. Both tissue vitamin E retention and biomarkers of chronic inflammation may be affected by the apoE genotype.

Elevated Levels of LDL-C are Associated With ApoE4 but Not With the rs688 Polymorphism in the LDLR Gene

“…The frequencies of ApoE isoforms were similar to ours in populations of countries like Ireland, 17 Germany, 18 United States 19 (P > .05), and ApoE4 isoform was significantly different in populations from France, Portugal, Spaind, 17 and Lebanon 20 (P < .05). These differences can be explained by the genetic diversity among populations.…”

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

“…Furthermore, degradation of vitamin E may be increased in the apoE e4 genotype contributing to lower tissue retention and therefore possibly lower vitamin E status in peripheral tissues (104) .…”

Using Individual, ApoE Genotype-Based Dietary and Physical Activity Advice to Promote Healthy Lifestyles in Finland—Impacts on Cardiovascular Risk Markers

“…In addition, carriers of apoE 4 allele have 3 -4 fold (genotype 3/4) and 12 -16 fold (genotype 4/4) increased risk of Alzheimer's disease [16]. ApoE affects cholesterol absorption, lipid metabolism and have function in vitamin E metabolismand the immune system [17]. It has been demonstrated that carriers of at least one apoE Ɛ4 allele have a higher cholesterol count, but better response to dietary changes (e.g.…”