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

Abstract

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 Ͼ 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 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.

Proteomic Analysis of Human Plasma during Intermittent Fasting

“…Several human protein-coding SNPs of APOA4 have been associated with clinical phenotypes, which includes the N147S variant detected in this study that is associated with the response to fenofibrate treatment . Another phenotype associated with several APOA4 variants is altered plasma total triacylglycerol abundance, , which is in agreement with our correlation analysis.…”

APOA4 Polymorphism as a Risk Factor for Unfavorable Lipid Serum Profile and Depression: A Cross-Sectional Study

“…In addition, our sample is an admixed population from Brazil and His-allele has been proposed as a marker of European admixture 41 ; hence, it could be modifying our results. Concerning serum levels, we observed that 360His allele showed reduced HDL and higher VLDL and TG levels, which might be due to delayed postprandial clearance of TG-rich lipoprotein 42 and may be a risk factor for metabolic disease.…”

APOA1/C3/A4/A5 Gene Cluster at 11q23.3 and Lipid Metabolism Disorders: From Epigenetic Mechanisms to Clinical Practices

“…Common APOA4 mutations include N147S, T347S, and Q360H [ 83 ]. A study by Hockey et al showed that the 360H allele has greater lipid affinity compared with 360Q [ 84 ]. APOA4 also has an anti-atherosclerotic effect.…”