Genes associated with hypercholesterolaemia have been detected and characterised at the loci for low density lipoprotein (LDL) receptor, apolipoprotein B, apolipoprotein E, and apolipoprotein (a) (Goldstein & Brown, 1989; Soria et al., 1989; Mahley & Rail, 1989; Utermann, 1989). Among them, genes at the loci for apolipoprotein E and apolipoprotein (a) are polymorphic and act as polymeric genes for multifactorial hypercholesterolaemia. These polymorphic genes have been identified by the analysis of proteins using electrophoretic methods. It is interesting to examine whether these polymorphic and seemingly deleterious genes are identical at the DNA and amino acid sequence levels among different ethnic groups. On the other hand, deleterious genes detected at the loci for LDL receptor and apolipoprotein B are not polymorphic but act as major genes which cause autosomal dominant hypercholesterolaemia. These genes have been shown to be a cause of premature coronary heart disease (Goldstein & Brown, 1989; Soria et al., 1989). The data obtained by the analysis of DNA suggest the same mutational origin for some of these deleterious genes (Goldstein & Brown, 1989) and their subsequent spread in populations.

This communication reports the results of molecular genetic studies on the phenotype E4 determined by the alleles at the locus for apolipoprotein E and on familial hypercholesterolaemia caused by the mutant LDL receptor gene in the Japanese population.

Apolipoprotein E4 in the Japanese population

Apolipoprotein E is a protein constituent of plasma lipoproteins and plays an important role in lipoprotein metabolism (Mahley, 1988). The genetic polymorphism of apolipoprotein E is under the control of three common alleles (ε2, ε3, ε4) that specify isoforms apolipoprotein E2, E3 and E4 respectively (Mahley & Rail, 1989).