Apoprotein E3-Leiden: A Variant of Human Apolipoprotein E3 Associated with Familial Type III Hyperlipoproteinemia

Abstract

As determined with isoelectric focusing, human apo E can be saparated into three major isoforms, i.e. E2, E3 and E4 and a number of minor glycosylated isoforms (1,2). The heterogeneity of apo E is proposed to be the result of different apo E alleles, at one single genetic locus (1,2,3). At present a number of apo E variants have been described (for reference see 4). Most of these variants are the underlying metabolic defect in familial type III HLP due to a more or less pronounced defect of these variants in binding to the hepatic lipoprotein receptors (5,6). It is reported that the potential receptor binding region of the apo E molecule lies between residues 126 and 218 (7,8). Most of the type III HLP patients exhibit the apo E2 (Arg₁₅₈→Cys) or E2 (Arg₁₄₅→Cys) variant. Recently, we described a type III HLP patient (C.V.) with apolipoprotein phenotype E3/3 as evaluated by isoelectric focusing (9). We reported that apo E3 from patient C.V. was defective in binding to the LDL receptor on cultured fibroblasts at 4°C, as compared with apo E3 isolated from a type IV HLP patient. In this paper we describe the partial characterization and the mode of inheritance of this defective apo E3, denoted apo E3-Leiden.