Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance.
Apolipoprotein (apo)A-IV is synthesized in the small intestine during fat absorption and is incorporated onto the surface of nascent chylomicrons. In circulation, apoA-IV is displaced from the chylomicron surface by high density lipoprotein-associated C and E apolipoproteins; this exchange is critical for activation of lipoprotein lipase and chylomicron remnant clearance. The variant allele A-IV-2 encodes a Q360H polymorphism that increases the lipid affinity of the apoA-IV-2 isoprotein. We hypothesized that this would impede the transfer of C and E apolipoproteins to chylomicrons, and thereby delay the clearance of postprandial triglyceride-rich lipoproteins. We therefore measured triglycerides in plasma, S(f) > 400 chylomicrons, and very low density lipoproteins (VLDL) in 14 subjects heterozygous for the A-IV-2 allele (1/2) and 14 subjects homozygous for the common allele (1/1) who were fed a standard meal containing 50 gm fat per m(2) body surface area. All subjects had the apoE-3/3 genotype. Postprandial triglyceride concentrations in the 1/2 subjects were significantly higher between 2;-5 h in plasma, chylomicrons, and VLDL, and peaked at 3 h versus 2 h for the 1/1 subjects. The area under the triglyceride time curves was greater in the 1/2 subjects (plasma, P = 0.045; chylomicrons, P = 0.027; VLDL, P = 0.063). A post-hoc analysis of the frequency of the apoA-IV T347S polymorphism suggested that it had an effect on triglyceride clearance antagonistic to that of the A-IV-2 allele. We conclude that individuals heterozygous for the A-IV-2 allele display delayed postprandial clearance of triglyceride-rich lipoproteins.
Hockey
K J
KJ
Section of Gastroenterology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Anderson
R A
RA
Cook
V R
VR
Hantgan
R R
RR
Weinberg
R B
RB
D000328:Adult; D001054:Apolipoproteins A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood*
D001054:Apolipoproteins A; D014280:Triglycerides; C022205:apolipoprotein A-IV