Role of apolipoprotein E and B gene variation in determining response of lipid, lipoprotein, and apolipoprotein levels to increased dietary cholesterol.
A large segment of the population is modifying its dietary cholesterol intake to achieve a healthier life-style. However, all individuals do not respond equally. We have investigated the effects that that two physiologically important polymorphisms in the apolipoprotein (apo) E and B genes have on the responses of plasma lipid, lipoprotein, and apolipoprotein levels to a high-cholesterol diet. Over a 6-wk period, individuals were prescribed two diets, one consisting of 300 mg dietary cholesterol/d for 3 wk and one consisting of 1,700 mg dietary cholesterol/d for 3 wk. Total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and apo B levels were significantly increased on the high-cholesterol diet. Average total cholesterol (numbers in parentheses are SDs) went from 167.6 (23.4) mg/dl on the low-cholesterol diet to 190.8 (36.2) mg/dl on the high-cholesterol diet; LDL-C went from 99.9 (24.8) mg/dl to 119.2 (33.4) mg/dl, and apo B went from 74.9 (24.5) mg/dl to 86.8 (29.5) mg/dl. In 71 individuals, the frequencies of the apo epsilon 2, epsilon 3, and epsilon 4 alleles were .09, .84, and .07, respectively. The frequency of the longer, apo B signal peptide allele (5'beta SP27) was .68. Apo epsilon 2/3 individuals had significantly lower LDL-C levels than did epsilon 3/3 homozygotes, on both the low-cholesterol diet (LDL-C lower by 21 mg/dl) and the high-cholesterol diet (LDL-C lower by 27 mg/dl). Average triglyceride levels were significantly different among apo B signal peptide genotypes, with the 5'beta SP27/37 homozygotes having the lowest levels (70 mg/dl). When individuals were switched from the low-cholesterol diet to the high-cholesterol diet, in no case were the average responses in lipid levels significantly different among apo E or B genotypes. Therefore, these gene loci do not have a major effect on the response of lipid levels to increased dietary cholesterol.
Boerwinkle
E
E
Center for Demographic and Population Genetics, University of Texas Health Science Center, Houston 77225.
Brown
S A
SA
Rohrbach
K
K
Gotto
A M
AM
Patsch
W
W
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D001835:Body Weight; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004036:Diet, Atherogenic; D014644:Genetic Variation; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008074:Lipoproteins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins