Apoprotein E serves important functions in the recognition of triglyceride-rich lipoprotein remnants by hepatic and peripheral cells. The """"""""wild type"""""""" apoE molecule (apoE3) binds to cellular apoB, E receptors with greater affinity than does LDL, whereas the interactions of certain mutant apoE molecules (e.g., apoE2) with cells are grossly impaired. The hypothesis to be tested is that the plasma lipoproteins of individuals who are apoE2/E3 heterozygotes are more responsive to alterations of dietary lipids than are the plasma lipoproteins of otherwise similar individuals who are apoE3/E3 homozygotes. Plasma lipoproteins will be characterized in the two groups of subjects while they are eating habitual, basal and high fat, high cholesterol experimental diets, using zonal ultracentrifugation and gel permeation column chromatography. Plasma lipoprotein lipids and apoprotein concentrations will be quantified and lipid and apoprotein compositions of lipoprotein fractions will be obtained. ApoE2/E3 heterozygotes comprize about 25% of the American population. Therefore, if apoE2/E3 heterozygotes turn out to be diet """"""""hyperresponders"""""""", an important segment of the population presumably at higher than average risk for the development of diet-related atherosclerosis will have been identified. Steps then can be taken to find and intervene on such individuals. A secondary hypothesis relating to the responsiveness of plasma lipoproteins to changes in dietary patterns of young and older subjects also will be tested, if time and resources permit.
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