Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans.
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.
Weinberg
R B
RB
Section of Gastroenterology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Geissinger
B W
BW
Kasala
K
K
Hockey
K J
KJ
Terry
J G
JG
Easter
L
L
Crouse
J R
JR
D001054:Apolipoproteins A / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology*; D005838:Genotype; D006801:Humans
D001054:Apolipoproteins A; D004041:Dietary Fats; C022205:apolipoprotein A-IV; D002784:Cholesterol