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

Journal of Lipid Research

Roy R. Hantgan¹  Karen J. Hockey²  Rachel A. Anderson²  Victoria R. Cook²  Richard B. Weinberg³ 

[1] Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157;Section of Gastroenterology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157;To whom correspondence should be addressed.;

关键词: genetic polymorphisms;    low density lipoproteins;    high density lipoproteins;    saturated fat;    polyunsaturated fat;    apolipoprotein E;   

DOI  :  

来源: DOAJ

【 摘 要 】

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, Sf > 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 posthoc 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.

【 授权许可】

Unknown