Apo E Genotyping: Cardiovascular Risk

Type III hyperlipoproteinemia (broad β disease) is a familial dyslipidemia characterized by the combination of elevated serum cholesterol and triglycerides and the presence of the apolipoprotein E (Apo E) genotype E2/E2. Type III hyperlipoproteinemia has an incidence of 1/2,000−1/10,000. This lipid disorder is associated with a high risk of coronary heart disease and peripheral vascular disease. Onset of type III hyperlipoproteinemia is generally in adulthood but varies from late teens to old age. Before vascular disease develops there are usually no symptoms, and most patients with type III hyperlipoproteinemia are identified only from elevated serum cholesterol and triglycerides discovered during a routine screen. Symptoms include angina, heart attack, claudication, and leg pain. In untreated patients, xanthomas (fat deposits) are occasionally seen (flat in palmar creases or tuberous in joints).

The E2 variant of apolipoprotein E is defective in binding to receptors that normally clear harmful lipid particles called B-VLDL from the circulation. One percent of the general population has the E2/E2 genotype, and development of the frank lipid disorder occurs in 1% to 5% of these predisposed individuals, triggered by secondary genetic, hormonal or environmental factors. Ninety-five percent of patients with type III hyperlipoproteinemia are homozygous for E2. Demonstration of the E2/E2 genotype is essential for diagnosis of type III hyperlipoproteinemia.

Distinguishing this disorder from other causes of elevated cholesterol is important because effective treatment of type III hyperlipoproteinemia to prevent atherosclerosis often requires a different approach than treatment of other dyslipidemias.