Genetics of lipoprotein disorders.

Abstract

Lipoproteins are circulating complexes of lipids and proteins, the transport and metabolism of which are directly controlled by apolipoproteins A-I, A-II, A-IV, B, C-I, C-II, C-III, D, E, and (a); lipoprotein-processing proteins lipoprotein lipase, hepatic lipase, lecithin-cholesterol acyltransferase, and cholesteryl ester-transfer protein; and lipoprotein receptors, low density lipoprotein (LDL) receptor, chylomicron remnant receptor, and scavenger receptors. Studies have shown a close association between lipoprotein abnormalities and coronary artery disease susceptibility. Four types of abnormalities are frequently seen: increased LDL cholesterol levels; decreased high density lipoprotein cholesterol levels, usually accompanied by increased triglyceride or very low density lipoprotein levels; increased concentrations of chylomicron remnants and intermediate density lipoproteins; and increased concentrations of an abnormal lipoprotein, lipoprotein (a). One or more of these abnormalities is present in 50-80% of myocardial infarction survivors. The exact pathogenic process whereby each of these abnormalities causes coronary artery disease is a subject of active investigation but beyond the scope of this brief presentation. However, the genetic contribution to each of these abnormal lipoprotein phenotypes is coming into focus and is discussed.