Polymorphism of Apolipoprotein E

Abstract

Plasma cholesterol levels are under multifactorial control. Environmental as well as genetic factors contribute to the considerable variance of cholesterol concentrations within and in between populations. Individual genes responsible for the normal variance of cholesterol in plasma have however not yet been identified. Conceptually such gene loci should be polymorphic and certain combinations of these genes may lead to polygenic familial hypercholesterolemia. On the other hand conditions are known where one rare mutant gene drastically affects the concentration of plasma lipids. Carriers of those genes have a monogenic familial dyslipoproteinemia. Among those are familial hypercholesterolemia, abetalipoproteinemia, Tangier disease, familial LCAT-deficiency and familial hyperchylomicronemia. Hence rare mutant genes, polymorphic gene loci and environmental factors have to be considered as determinants of plasma lipid levels. This makes the plasma lipoprotein system an excellent model to study the interaction of genes and environment in producing a multifactorial disease. Mutations resulting in familial dys1ipoproteinemia may afflict: 1. the synthesis, assembly and secretion of lipoproteins, 2. the structure of apolipoproteins, 3. enzymes involved in the interconversion and intravasal catabolisra of lipoproteins (lipase, LCAT) and 4. recognition, uptake and degradation of lipoproteins by cells. The same gene loci afflicted in familial dysiipoproteinemia also have to be considered responsible for normal genetic variance of plasma lipid and lipoprotein levels.