Polymorphism of apolipoprotein E

Apolipoprotein E from human serum shows a genetic polymorphism determined by two autosomal codominant alleles, Apo En and Apo Ed. Homozygosity for the gene Apo Ed (phenotype Apo E‐D) results in primary dysbetalipoproteinemia, but only some individuals with this phenotype develop gross hyperlipidemia (hyperlipoproteinemia type III). Vertical transmission of dysbetalipoproteinemia represents pseudodominance due to the high frequency of the gene Apo Ed. Dysbetalipoproteinemia is already expressed in childhood.To assess the influence of other genes on the expression of hyperlipidemia in phenotype Apo E‐D, comparative studies were carried out in kindreds of hypercholesterolemic (group A) and normo‐ or hypocholesterolemic probands with dysbetalipoproteinemia (group B). This demonstrated the occurrence of familial (non‐type III) forms of hyperlipidemia in group A but not in group B kindreds. Distribution of lipoprotein pheno‐types in five of the group A kindreds was consistent with the occurrence of familial combined hyperlipidemia. Apo E phenotypes and hyperlipidemia segregated independently.It is concluded that primary dysbetalipoproteinemia is a frequent monogenic variant of lipoprotei