SIMULTANEOUS EFFECTS OF THE APOLIPOPROTEIN-E POLYMORPHISM ON APOLIPOPROTEIN-E, APOLIPOPROTEIN-B, AND CHOLESTEROL-METABOLISM

  • 1 January 1988
    • journal article
    • research article
    • Vol. 42  (1) , 104-112
Abstract
Human apolipoprotein (apo) E is polymorphic. We have investigated the effect of the apo-E polymorphism on quantitative levels of apo E, apo B, and total cholesterol in a sample of 563 blood-bank donors from Marburg and Giessen, West Germany. The relative frequencies of the .epsilon.2, .epsilon.3, and .epsilon.4 alleles are .063, .793, and .144, respectively. The average effects of the .epsilon.2 allele are to raise apo-E levels by 0.95 mg/dl, lower apo B levels by 9.46 mg/dl, and lower total cholesterollevels by 14.2 mg/dl. The average effects of the .epsilon.4 allele are to lower apo-E leveles by 0.19 mg/dl, to raise apo-B levels by 4.92 mg/dl, and to raise total cholesterol levels by 7.09 mg/dl. The average effects of the .epsilon.3 allele are near zero for all three phenotypes. The apo-E polymorphism accounts for 20% of the variability of plasma apo-E levels, 12% of the variability of plasma apo-B levels, and 4% of the variability of total plasma cholesterol levels. The inverse relationship between the genotype-specific average apo-E levels and both the genotypic-specific average apo-B and cholesterol levels is offset by a positive relationship between apo-E levels and both apo-B and cholesterol levels within an apo-E genotype. The apo-E polymorphism also has a direct effect on the correlation between apo-E and total cholesterol levels. The implication of these results on multivariate genetic analyses of these phenotypes is discussed. On the basis of these results we propose a model for the effect of the apo-E polymorphism on lipid metabolism in normolipidemic subjects. According to this model, the primary effect of the apo-E polymorphism is on the metabolism of apo E-containing lipoprotein particles. The reported effects of this polymorphism on other lipoprotein fractions and total serum cholesterol levels is mediated through apo-B/apo-E receptor regulation.

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