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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:289.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Postprandial Plasma ApoB-48 Levels Are Influenced by a Polymorphism in the Promoter of the Microsomal Triglyceride Transfer Protein Gene

Björn Lundahl; Anders Hamsten; Fredrik Karpe

From the Atherosclerosis Research Unit (B.L., A.H., F.K.), King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital, Stockholm, Sweden, and the Oxford Lipid Metabolism Group (F.K.), Oxford Centre for Diabetes, Metabolism, and Endocrinology, Oxford, UK.

Correspondence to Dr Fredrik Karpe, Oxford Lipid Metabolism Group, Radcliffe Infirmary, Oxford OX2 6HE, UK. E-mail fredrik.karpe{at}oxlip.ox.ac.uk

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.

Key Words: genetic variability • DNA bank • genetic screening • complex phenotype • alimentary lipemia

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