Simultaneous effects of the apolipoprotein E polymorphism on apolipoprotein E, apolipoprotein B, and cholesterol metabolism.
Human apolipoprotein (apo) E is polymorphic. We have investigated the effect of the apo-E polymorphism on quantitative plasma 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 cholesterol levels by 14.2 mg/dl. The average effects of the epsilon 4 allele are to lower apo-E levels 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 genotype-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Boerwinkle
E
E
Center for Demographic and Population Genetics, University of Texas Health Science Center, Houston 77025.
Utermann
G
G
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001055:Apolipoproteins B / Q000097:blood*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D002784:Cholesterol