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Journal of Lipid Research, Vol. 42, 211-217, February 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance

Correspondence to: Richard B. Weinberg, To whom correspondence should be addressed., weinberg{at}wfubmc.edu (E-mail)

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 m² 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., R. A. Anderson, V. R. Cook, R. R. Hantgan, and R. B. Weinberg. Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance. J. Lipid Res. 2001. 42: 211;–217.

Supplementary key words: genetic polymorphisms, low density lipoproteins, high density lipoproteins, saturated fat, polyunsaturated fat, apolipoprotein E

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