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. ApoE allele frequencies show non-random global distribution especially in Europe with high apoE e3 frequency in the Mediterranean area, whereas the apoE e4 genotype is enriched in Northern Europe. The apoE e4 genotype 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 the apoE e3 but not the apoE e4 genotype may significantly benefit from dietary flavonoids (e.g. quercetin) and n-3 fatty acids. Metabolism of lipid soluble vitamins E and D is likewise differentially affected by the apoE genotype. Epidemiological and experimental evidence suggest a better vitamin D status in apoE e4 than e3 subjects indicating a certain advantage of e4 over e3. The present review aims at evaluation of current data available on interactions between apoE polymorphism and dietary responsiveness to flavonoids, fat soluble vitamins and n-3 fatty acids. Likewise, distinct geographic distribution and chronic disease risk of the different apoE isoforms are addressed.

Association of the ApoE gene polymorphism and dietary factors with cerebral infarction and circulating lipid concentrations

“…Research data showed that the ApoE polymorphism had a highly significant impact on lipid concentrations (Petkeviciene et al, 2012;Rudkowska et al, 2013). However, environmental factors, including living conditions, diet, and living habits, were also shown to affect blood lipid levels and cerebral infarction (CI) (Egert et al, 2012;Petkeviciene et al, 2012;Rudkowska et al, 2013). Therefore, this study focused on the relationship between the ApoE gene polymorphism and dietary factors in the association with plasma lipid concentrations.…”

Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer’s Disease

“…It has been well established that apolipoprotein E (ApoE) is a very important genetic risk factor for age-dependent chronic diseases, including CVD and AD [12]. Due to two major polymorphisms on the encoding exon 4 of this gene, three major protein isoforms, ApoE ε2, ApoE ε3 and ApoE ε4 exist [13]. It has been shown that homozygous carriers of the ApoE ε4 allele have a more than 10-fold increased risk of developing AD, possibly due to increased cholesterol levels, altered brain development early in life [12] or increased oxidative brain damage [14].…”

The Relationship between Obstructive Sleep Apnea Syndrome and Apolipoprotein E Genetic Variants

“…Although these allelic forms differ from each other by only one or two amino acids at positions 112 and 158, these differences alter the APOE structure and function. There are 6 genotypes of APOE: E2/E2, E2/E3, E3/E3, E2/E4, E3/E4 and E4/E4 [11,12,13]. Their frequencies vary substantially around the world, but APOE3 is the most common almost everywhere and is often considered to be the ancestral or ‘wild-type' allele for that reason [14].…”