Apolipoprotein E Isoform Phenotype and LDL Subclass Response to a Reduced-Fat Diet

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Abstract
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.