APOE Genotyping: Cardio Risk

Apolipoprotein E (apoE) is a component of several lipoproteins. There are three main apoE isoforms reflecting three alleles (E2, E3 and E4), of which E3 is the most common. The APOE genotype E2/E2 is present in approximately 1% of the population and predisposes to type III hyperlipoproteinemia (dysbetalipoproteinemia). 

Type III hyperlipoproteinemia involves abnormal build-up in the blood of remnant chylomicrons and VLDL particles (collectively called B-VLDL) containing cholesterol and triglycerides. Excess B-VLDL is taken up in blood vessel walls and can lead to atherosclerosis. Therefore, individuals with type III hyperlipoproteinemia have high total serum cholesterol, LDL and triglycerides. The main clinical manifestation is premature atherosclerosis, leading to coronary artery disease or peripheral vascular disease. However, some patients may be asymptomatic.

Only 1% to 5% of individuals with the E2/E2 genotype develop type III hyperlipoproteinemia. However, the E2/E2 genotype is present in 95% of individuals with type III hyperlipoproteinemia and is diagnostic of the disorder in individuals with the appropriate lipid profile. A number of secondary factors are known to provoke type III hyperlipoproteinemia in individuals with the E2/E2 genotype, including glucose intolerance, diabetes mellitus, hypothyroidism, obesity, low estrogen levels and excessive alcohol intake.