HUMAN APOLIPOPROTEIN-E ISOPROTEIN SUBCLASSES ARE GENETICALLY-DETERMINED

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 33  (1) , 11-24
Abstract
Human, very low density lipoprotein (VLDL) apolipoprotein E (apoE) from different individuals appears on 2-dimensional gel electrophoretic analysis in 1 of 2 complex patterns, class .alpha. or class .beta.. Mixing of VLDL from different subjects revealed that not all .alpha. or .beta. apoE patterns were the same. In this manner, 3 subclasses of class .alpha. (.alpha.II, .alpha.III and .alpha.IV) and 3 subclasses of class .beta.(.beta.II .beta.III and .beta.IV) were identified. Family studies revealed that the subclasses (.alpha.II, .alpha.III and .alpha.IV and .beta.II, .beta.III and .BETA.IV) of apoE are determined at a single genetic locus with 3 common alleles.sbd..epsilon.II, .epsilon.III and .epsilon.IV. The class .beta. phenotypes (.beta.II, .beta.III and .beta.IV) represent homozygosity for 2 identical apoE alleles (.epsilon.). In contrast, class .alpha. phenotypes (.alpha.II, .alpha.III and .alpha.IV) represent heterozygosity for 2 different apoE alleles. The apoE subclasses and their corresponding genotypes are as follows: .beta.II = .epsilon.II/.epsilon.II; .beta.III = .epsilon.III/.epsilon.III; .beta.IV = .epsilon.IV/.epsilon.IV; .alpha.II = .epsilon.II/.epsilon.III; .alpha.III = .epsilon.III/.epsilon.IV; and .alpha.IV = .epsilon.II/.epsilon.IV. To estimate the frequencies of the apoE alleles in the general population, apoE subclasses were then investigated in 61 unrelated volunteers, and the results were .beta.II = 1 (2%), .beta.III = 30 (49%), .alpha.II = 9 (15%), .alpha.III = 19(31%) and .alpha.IV = 2(3%). Utilizing the frequencies of these phenotypes, the gene frequencies were calculated to be .epsilon.II = 11%, .epsilon.III = 72% and .epsilon.IV = 17%. ApoE subclasses were studied in a clinic for individuals with plasma lipid disorders, and the apoE subclass .beta.IV was associated with type III hyperlipoproteinemia. There was no association of any apoE subclass with type II, type IV or type VI hyperlipoproteinemia, or plasma HDL [high density lipoprotein] cholesterol levels. The genetic basis for the common variation in a human plasma protein, apoE, is explained.