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 a bsorption and is incorporated onto the surface of nascent chylomicrons, In circulation, apoA-IV is displaced from the chylomicron surface by high dens ity lipoprotein-associated C and E apolipoproteins; this exchange is critic al for activation of lipoprotein lipase and chylomicron remnant clearance, The variant allele A-IV-2 encodes a Q360H polymorphism that increases the l ipid 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 the refore measured triglycerides in plasma, S-f > 400 chylomicrons, and very l ow density lipoproteins (VLDL) in 14 subjects heterozygous for the A-IV-2 a llele (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 s ubjects had the apoE-3/3 genotype, Postprandial triglyceride concentrations in the 1/2 subjects were significantly higher between 2-5 h in plasma, chy lomicrons, 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 (p lasma, P = 0.045; chylomicrons, P = 0.027; VLDL, P = 0.063). A post-hoc ana lysis 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 dis play delayed postprandial clearance of triglyceride-rich lipoproteins.