Postprandial plasma ApoB-48 levels are influenced by a polymorphism in the promoter of the microsomal triglyceride transfer protein gene.
The microsomal triglyceride transfer protein (MTP) plays a key role in the secretion of apolipoprotein B (apoB)-containing lipoproteins. The rare variant of a functional polymorphism in the promoter region of the MTP gene has been associated with elevated transcriptional activity of the gene in vitro (MTP-493G/T). With use of a "recruit-by-genotype" approach, we investigated one of the potentially complex phenotypes of this polymorphism, the appearance in plasma of apoB-48 after a meal intake. A total of 12 homozygous carriers of the rare MTP-493T variant were identified from a population-based screening of 50-year-old healthy white men. All subjects were of the apoE3/3 genotype. Along with 48 baseline well-matched heterozygotes (n=24) plus homozygotes (n=24) for the common variant, they were given a standardized oral fat meal. Postprandial plasma concentrations of apoB-48 were determined by the combination of density gradient ultracentrifugation and analytical SDS-PAGE. The postprandial plasma concentrations of triglycerides did not differ between the groups, but homozygous carriers of the rare MTP-493T variant showed a >100% greater increase in apoB-48 in the smallest (Svedberg flotation rate constant 20 to 60) triglyceride-rich lipoprotein fraction (P=0.005). These data support the notion that elevated transcriptional activity of MTP leads to an increased generation of the smallest triglyceride-rich lipoprotein from the intestine.
Lundahl
Björn
B
Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Hamsten
Anders
A
Karpe
Fredrik
F
D000704:Analysis of Variance; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D019540:Area Under Curve; D002352:Carrier Proteins / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D019518:Postprandial Period / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values; D013548:Sweden; D014280:Triglycerides / Q000097:blood
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D004041:Dietary Fats; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein