Apolipoprotein E isoform phenotype and LDL subclass response to a reduced-fat diet.
We investigated the association of apolipoprotein (apo) E isoform phenotype with lipoprotein response to reduced dietary fat intake in 103 healthy men (apoE3/2, n = 10; apoE3/3, n = 65; and apoE4/3, 4/4, n = 28). In a randomized, crossover design, subjects consumed high-fat (46%) and low-fat (24%) diets for 6 weeks each. High-fat LDL cholesterol differed among phenotypes, with apoE4/3, 4/4 > apoE3/3 > apoE3/2. Reduction of LDL cholesterol on the low-fat diet was greater for apoE4/3, 4/4 than apoE3/3 (P < .05). There was no significant change in plasma apoB level within any of the apoE phenotype groups on the low-fat diet. This result, together with measurements of LDL subfraction mass by analytical ultracentrifugation, indicated that the primary basis for the diet-induced reduction in LDL cholesterol was not reduced LDL particle number but rather a shift from large, buoyant, cholesterol-rich LDL particles (flotation rate, 7 to 12) to smaller, denser LDL particles (flotation rate, 0 to 7). The magnitude of this effect was related to apoE phenotype, with progressively greater reductions in levels of large LDL (P < .01) from apoE3/2 to apoE3/3 to apoE4/3, 4/4. These results indicate that reduced dietary fat lowers levels of large, buoyant LDL particles by an apoE-dependent mechanism.
Dreon
D M
DM
Donner Laboratory, Lawrence Berkeley Laboratory, CA 94720, USA.
Fernstrom
H A
HA
Miller
B
B
Krauss
R M
RM
D001057:Apolipoproteins E / Q000097:blood* / Q000737:chemistry; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000008:administration & dosage*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D014461:Ultracentrifugation
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D004041:Dietary Fats; D008077:Lipoproteins, LDL