What is being tested?The test looks at a patient’s
DNA to determine what combination of Apo E gene alleles (copies) he or she has. The ApoE gene exists in three different forms – e2, e3, and e4 – with e3 considered to be the normal form. Everyone has a pair of ApoE genes that is some combination of these three.
Apolipoprotein (Apo) E is produced under the direction of the ApoE gene and is one of five main types of blood lipoproteins (A-E). It is created primarily in the liver and brain and has two primary metabolic roles: 1) transport of lipids from their site of synthesis, or absorption, to the tissues where lipids are stored or excreted, and 2) transport of lipids, in particular cholesterol, from the peripheral organs to the liver for excretion. Apo E also modulates the activity of enzymes involved in lipid and lipoprotein metabolism.
ApoE e3/e3 is the normal genotype (62% of population) without significant cardiovascular disease-environment association. ApoE e4 (e4/e4 and e4/e3, 25% of population) is associated with increased risk of atherosclerosis. These patients are predisposed to an exaggerated elevation of LDL-C when their diet is high in saturated fat. Patients with the ApoE e2 isoform tend to have lower LDL-C levels, while ApoE e2 and ApoE e4 are both associated with elevated triglyceride levels. If someone has an e2/e2 combination, they may clear dietary fat from their body at a slower rate and be at a higher risk for early vascular disease. If they have an e4/e4, they may be at higher risk of developing atherosclerosis. It is not a straightforward diagnosis, however, as other factors, such as obesity, diabetes, and hypothyroidism, may play a role in whether a patient actually develops disease.
ApoE e4 has also been associated with an increased risk of late onset Alzheimer’s disease (AD) (developing after the age of 65). This effect is additive in that one copy of e4 (e2/e4 or e3/e4) carries some increased risk and two copies of e4 (e4/e4) are associated with an even greater risk of developing AD. It must be remembered, however, that this risk is only relative. Most individuals with ApoE4 will never develop AD and there are many AD patients who are e4 negative.
