Study type: Blood collected in a gold-, red-, red/gray-, green- [heparin], or lavender-top [EDTA] tube; related body system: Circulatory system.

Normally, apolipoproteins assist in the regulation of lipid metabolism by activating and inhibiting enzymes required for this process. The apolipoproteins also help keep lipids in solution as they circulate in the blood and direct the lipids toward the correct target organs and tissues in the body. A number of types of apolipoproteins have been identified (A, B, C, D, E, H, J), each of which contains subgroups.

Apolipoprotein A (Apo A), the major component of high-density lipoprotein (HDL), is synthesized in the liver and intestines. Apo A-I activates the enzyme lecithin-cholesterol acyltransferase (LCAT), whereas Apo A-II inhibits LCAT. There is an inverse relationship between Apo A levels and risk for developing CAD. For additional information regarding screening guidelines for atherosclerotic cardiovascular disease (ASCVD), refer to the study titled “Cholesterol, Total and Fractions.” Because of difficulties with method standardization, the above-listed reference ranges should be used as a rough guide in assessing abnormal conditions. Values for people of African descent are 5 to 10 mg/dL (0.05–0.1 g/L) higher than values for individuals of European descent.

Apolipoprotein B (Apo B), the major component of the low-density lipoproteins (chylomicrons, low-density lipoprotein [LDL], and very-low-density lipoprotein [VLDL]), is synthesized in the liver and intestines. Most cases of hyperlipidemia result from the combined effects of unhealthy lifestyle choices and single or multiple gene mutations related to lipid metabolism. Genetic testing is available to identify the presence of inherited gene mutations associated with familial hypercholesterolemia. There are a number of genes associated with the potential for development of coronary artery disease (CAD), including APOB. Mutations have been identified in the LDLR gene (most commonly identified), APOB gene (low incidence, 5% or less), or PCSK9 gene (least commonly identified). Mutations in the PSCK9 gene are inherited in an autosomal dominant pattern. Mutations in the LDLRAP1 gene are inherited in an autosomal recessive pattern.

Apolipoprotein E is found in most lipoproteins, except LDL, and is synthesized in a variety of cell types, including liver, brain astrocytes, spleen, lungs, adrenals, ovaries, kidneys, muscle cells, and in macrophages. The largest amount is produced by the liver; the next significant amount is produced by the brain. There are three forms of Apo E: Apo-E2, Apo-E3, and Apo-E4, and six possible combinations; of these, Apo-E3 (e3/3e) is the fully functioning form. The varied roles of Apo E include removal of chylomicrons and VLDL from the circulation by binding to LDL. The Apo E2 isoform demonstrates significantly less LDL receptor binding, which results in impaired clearance of chylomicrons, VLDL, and triglyceride remnants. The presence of Apo E isoforms E2 and E4 is associated with high cholesterol levels, high triglyceride levels, and the premature development of atherosclerosis. The presence of the E2 isoform is associated with type III hyperlipidemia, a familial dyslipidemia, which is important to distinguish from other causes of hyperlipidemia to determine the correct treatment regimen. Apo E4 is being used in association with studies of predisposing factors in the development of Alzheimer disease. Additional information is found in the study titled “Alzheimer Disease Markers.”