Background Information:
Apolipoprotein E (ApoE) is a component of several lipoproteins involved in the metabolism and transport of lipids in the body, including chylomicrons, very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and high-density lipoproteins (HDL). ApoE plays a critical role in the transport and clearance of cholesterol and triglyceride-rich lipoproteins from the bloodstream, particularly by mediating their uptake by the liver through interaction with the LDL receptor family. ApoE also has important functions in lipid transport within the brain.
The APOE gene (Apolipoprotein E) provides instructions for making apolipoprotein E, located on chromosome 19q3.2. There are three APOE isoforms reflecting three alleles (E2, E3, E4). Three genotypes of the ApoE gene (ApoE ε2, ε3, ε4) are determined based on the combination of ApoE rs429358 and ApoE rs7412 SNPs located in the fourth exon of the ApoE gene, affect the amino acids at position 112 and 158 respectively.
The E3/E3 combination is the most common, and is associated with normal cholesterol levels
The apolipoprotein E (APOE) E2 isoform is associated with hyperlipoproteinemia type III, a rare condition that’s also known as dysbetalipoproteinemia or remnant removal disease.
Individuals with the E2/E2 genotype (about 1% of the general population) may have slower clearance of dietary fat. This genotype predisposes them to early vascular disease and type III hyperlipoproteinemia. However, only 1% to 5% of those with the E2/E2 genotype develop the full lipid disorder, often triggered by other factors like genetics, hormones, diet, or age.
The vast majority (95%) of patients with type III hyperlipoproteinemia are homozygous for E2, confirming the E2/E2 genotype is crucial for diagnosing type III hyperlipoproteinemia.
Individuals with the APOE ε4/ε4 genotype may have greater cholesterol and low-density lipoprotein (LDL) levels in the blood. This is due to altered lipid metabolism and reduced efficiency in lipid clearance compared to ApoE3. The elevated LDL cholesterol predisposes them to atherosclerosis and higher risk of developing Coronary Heart Disease (CHD) and other cardiovascular diseases.
Hyperlipoproteinemia Type III (HPL III) is characterized by elevated levels of both cholesterol and triglycerides, the accumulation of β-VLDL (remnant lipoproteins), and the presence of xanthomas. It is associated with an increased risk of premature atherosclerosis, including coronary heart disease (CHD) and peripheral artery disease (PAD). The condition is influenced by a combination of genetic factors—most notably homozygosity for the APOE ε2 allele (ε2/ε2 genotype) and non-genetic (lifestyle and environmental) factors such as obesity, diabetes, and hypothyroidism. The estimated incidence of HPL III is approximately 1 in 5,000 individuals in the general population.
Test Limitations:
This assay detects only the two common APOE polymorphisms (rs429358 and rs7412) that define the ε2, ε3, and ε4 alleles. Rare variants or other genetic and non-genetic factors influencing lipid metabolism will not be detected.