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 ( approximately 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.
Highlights
We investigated the effect of the A-IV-2 allele, which encodes a Q360H substitution in apolipoprotein A-IV, and dietary fat on cholesterol absorption in humans
In two studies in which the subjects consumed ad libitum diets, fractional cholesterol absorption was found to be lowest in subjects carrying an apoE2 allele, intermediate in apoE3/3 subjects, and highest in subjects with E3/4 or E4/4 phenotypes [22, 23]
Our data establish that subjects heterozygous for the A-IV-2 allele have lower fractional cholesterol absorption than A-IV-1/1 homozygous subjects on a high cholesterol, high polyunsaturated fat diet
Summary
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 (ϳ800 mg/day) diets with different fatty acid compositions. A post hoc analysis of the effect of the apoA-IV T347S polymorphism across all diets revealed a Q360H ϫ 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. Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans.
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