APOE is a member of the apolipoprotein family which confers metabolic control of lipoproteins and is associated with lipid transport ^[4] It also has additional roles as a cell-specific multifunctional protein necessary for the immune system, adipose tissue and the brain ^[5].

• Immune system – Human monocytes differentiate into macrophages becoming one of two main types, either pro-inflammatory macrophages (M1) or anti-inflammatory macrophages (M2). ApoE is associated with mature anti-inflammatory M2 macrophages found in the periphery of the body. Its roles have been investigated in both mouse and human models and found to include inhibition and clearance of atherosclerotic of foam cells and anti-inflammatory effects ^[6].
• Adipose tissue – Mature adipocytes express ApoE, and this is higher in subcutaneous fat compared to visceral fat. Roles in humans are linked to increased cell fat uptake and size, with a possible link to inflammation and insulin sensitivity^[6].
• Brain – ApoE is expressed throughout the brain and thought to have a role in brain homeostasis via delivery of lipoproteins by astrocytes to neurons influencing lipid metabolism and is linked with Alzheimer’s disease risk ^[4].

The APOE gene is located on chromosome 19 and contains instructions for making ApoE protein. Two genetic variations SNPs (rs429358 and rs7412) in the APOE gene are used together to define three variants (known as alleles) of known as E2, E3, and E4. Everyone inherits two APOE genes, one from each parent. Therefore it is possible to have one of the following six genotypes, E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, E4/E4. While an E3/E3 genotype is by far the most common form in the human population, ancestry results indicate that ApoE4 is the ancestral allele, more prevalent in indigenous people of Central Africa, Oceania and Mexico ^[8]. The changes to the amino acid code of the ApoE4 allele means that this variant is more compact and unstable, reducing its function, the implications of which are still being elucidated. A common theme is its structural change reducing functionality and this impacting, brain health, cardiovascular health, inflammation and risk of weight gain and reducing longevity ^[8].

Nutritional factors are known to influence APOE, such as omega 3 essential fatty acids. Having an inappropriate balance (inflammatory) of omega 3 Essential Fatty Acids is associated with reduced cognitive decline, cardiovascular disease and longevity in the general population. Research has noted that this important dietary nutrient may especially benefit those with the ApoE4 alleles for the prevention of cognitive decline and Alzheimer’s disease 7. Although the biological mechanisms for this association are not clear, likely candidates are that omega 3 presence in brain lipid membranes increases functionality and helps to counteract anti-inflammatory effects of ApoE4. In line with the evidence that ApoE4 mediates an inflammatory impact, promotion of anti-inflammatory lifestyle interventions should be encouraged for E4 allele carriers.

At myDNAhealth, we embrace a philosophy of ‘Precision Nutrition’ a relatively new term which is considered as a way to use genomics information to personalise nutritional and lifestyle advice. The Optimal Health report analyses genetic variations such as APOE plus inflammatory lifestyle factors using a user-friendly online platform. As a practitioner, this allows you to assess how these influence an individuals biology, to optimise advice and promote health at a personal level.

If you would like to take you knowledge and understanding of Precision Nutrition, consider enrolling on our unique digital educational programme – Molecular & Personalised Nutritional Genomics.