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

Abstract

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 × 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.

Keywords

• genetic polymorphisms
• low density lipoproteins
• high density lipoproteins
• saturated fat
• polyunsaturated fat
• apolipoprotein E