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

Abstract

ApoE is a key protein in lipid metabolism with three major isoforms.ApoEallele frequencies show non-random global distribution especially in Europe with highapoEε3frequency in the Mediterranean area, whereas theapoEε4genotype is enriched in Northern Europe. TheapoEε4genotype is one of the most important genetic risk factors for age-dependent chronic diseases, including CVD and Alzheimer's disease (AD). The apoE polymorphism has been shown to impact on blood lipids, biomarkers of oxidative stress and chronic inflammation, which all may contribute to the isoform-dependent disease risk. Studies in mice and human subjects indicate that theapoEε3but not theapoEε4genotype may significantly benefit from dietary flavonoids (e.g. quercetin) andn-3 fatty acids. Metabolism of lipid soluble vitamins E and D is likewise differentially affected by theapoEgenotype. Epidemiological and experimental evidence suggest a better vitamin D status inapoEε4than ε3subjects indicating a certain advantage of ε4over ε3. The present review aims at evaluation of current data available on interactions between apoE polymorphism and dietary responsiveness to flavonoids, fat soluble vitamins andn-3 fatty acids. Likewise, distinct geographic distribution and chronic disease risk of the different apoE isoforms are addressed.