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Journal of Lipid Research, Vol. 41, 2035-2041, December 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans

Correspondence to: Richard B. Weinberg

We investigated the effect of the A-IV-2 allele, which encodes a Q360H substitution in apolipoprotein (apo) A-IV, and dietary fat on cholesterol absorption in humans. In three separate studies we compared fractional intestinal cholesterol absorption between groups of subjects heterozygous for the A-IV-2 allele (1/2) and homozygous for the common allele (1/1) receiving high cholesterol (800 mg/day) diets with different fatty acid compositions. All subjects had the apoE 3/3 genotype. There was no difference in cholesterol absorption between the two genotype groups receiving a high saturated fat diet (33% of total energy as fat; 18% saturated, 3% polyunsaturated, 12% monounsaturated) or a low fat diet (22% of total energy as fat; 7% saturated, 7% polyunsaturated, 8% monounsaturated) diet. However, on a high polyunsaturated fat diet (32% of total energy as fat; 7% saturated, 13% polyunsaturated, 12% monounsaturated) mean fractional cholesterol absorption was 56.7% ± 1.9 in 1/1 subjects versus 47.5% ± 2.1 in 1/2 subjects (P = 0.004). A post hoc analysis of the effect of the apoA-IV T347S polymorphism across all diets revealed a Q360H x T347S interaction on cholesterol absorption, and suggested that the A-IV-2 allele lowers cholesterol only in subjects with the 347 T/T genotype.

We conclude that a complex interaction between apoA-IV genotype and dietary fatty acid composition modulates fractional intestinal cholesterol absorption in humans. — Weinberg, R. B., B. W. Geissinger, K. Kasala, K. J. Hockey, J. G. Terry, L. Easter, and J. R. Crouse. Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans. J. Lipid Res. 2000. 41: 2035;–2041.

Supplementary key words: genetic polymorphisms, low density lipoproteins, high density lipoproteins, saturated fat, polyunsaturated fat, apolipoprotein E, dual-isotope method

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