Apolipoprotein E (apo E) is one of the major protein constituents in VLDL and has been thought to play an important role in lipoprotein metabolism. We analyzed heterogeneity of apo E in VLDL from patients with hyperlipidemia and/or atherosclerosis by isoelectric focusing (IEF).
Six different apo E phenotypes were shown by IEF in agreement with the current genetic model that the major apo E isoproteins, apo E-4, apo E-3 and apo E-2, resulted from three apo E alleles, ε4, ε3 and ε2, at a single genetic locus. All the patients with broad-β disease (classical type III hyperlipoproteinemia) were confirmed to have the E2/2 phenotype representing homozygosity for ε2 allele.
We recognized an additional apolipoprotein band basic to apo E-IV in three subjects. The new apolipoprotein component was identical with ordinary apo E with regard to an apparent molecular weight by SDS-polyacrylamide gel electrophoresis and to the interaction with Heparin-Sepharose gel as well as anti-apo E antibody. This mutant apo E isoprotein, named apo E-5, was shifted more basic isoelectric point by one unit of charge than apo E-4 isoprotein. Genetic analysis of the apo E phenotypes in family members of the patients with apo E-5 indicated the presence of a new apo E allele (ε5) at the same genetic locus as former alleles. Since many of the subjects with apo E-5 had ischemic heart disease or cerebral infarction, it was suggested that the mutant apo E possibly related to the genesis of atherosclerosis.
