Humans display a heterogeneous response to dietary cholesterol; the etiology of this differential response is not known, but may involve genetic polymorphisms of the plasma apolipoproteins A-IV is a plasma glycoprotein of intestinal origin which may play a major role in the absorption and intravascular metabolism of cholesterol. A common genetic polymorphism apo A-IV, apo A-IV-2, has been identified, and recent work by the principal investigator has established that apo A-IV-2 displays unique structural and functional characteristics which may a cause a distinctive and salutary response to dietary cholesterol in individuals heterozygous for the mutant gene. It is the purpose of this study to investigate the effect of the apo A-IV-2 allele on the response of serum lipids and apolipoproteins to high cholesterol diets by a direct comparison of a group of subjects who are heterozygous for the apo A-IV-2 mutation, and a matched group of normal subjects. The finding of significant differences in response between the two groups would yield new insight into the factors regulating the human response to dietary cholesterol, provide further clues to the specific function of apo A-IV in human lipid metabolism, and have important implications for the dietary therapy of patients with hyperlipidemia.
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