Apolipoproteins, quantitative lipoprotein traits and multifactorial hyperlipidaemia

Genetic polymorphism and rare mutants of apolipoproteins occur in humans. The polymorphism of apolipoprotein E (apoE) is controlled by three common alleles, epsilon 2, epsilon 3, and epsilon 4, which code for proteins that differ in lipoprotein receptor binding activity, or in their catabolism in vivo, or both. This may explain the observed significant effects of the apoE alleles on the phenotypic variance of plasma lipoprotein concentrations in different ethnic groups and, moreover, the involvement of apoE alleles in the pathogenesis of multifactorial forms of hyperlipidaemia, for example, hypertriglyceridaemia, familial type III hyperlipidaemia (apoE-2 Arg-158----Cys) and polygenic hypercholesterolaemia (apoE-4 Cys-112----Arg). A further polymorphic gene locus controls the concentrations of the Lp(a) lipoprotein complex in plasma, which may vary from less than 1 mg/dl to greater than 200 mg/dl between different individuals. This lipoprotein contains two different polypeptides, apoB-100 and the Lp(a) glycoprotein. The Lp(a) glycoprotein exhibits genetic polymorphism which is controlled by a series of autosomal alleles at a single locus and which is associated with lipoprotein concentrations in plasma. This suggests that the same gene locus is involved in determining Lp(a) glycoprotein phenotypes and Lp(a) lipoprotein concentrations in plasma. Thus, there is evidence that variability in apolipoprotein genes relates to the normal variance of lipoprotein concentrations in the population and that this variability is a major genetic factor in multifactorial forms of hyperlipidaemia.