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Journal of Lipid Research, Vol. 40, 1686-1694, September 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

A functional polymorphism in the apolipoprotein B promoter that influences the level of plasma low density lipoprotein

Correspondence to: Ferdinand M. van 't Hooft

Apolipoprotein (apo) B is the structural protein moiety of plasma low density lipoprotein (LDL), an important risk factor for coronary heart disease (CHD). There is evidence that the rate of synthesis of apoB-containing lipoproteins may play an important role in the regulation of plasma LDL levels. However, it is generally thought that transcriptional regulation of the apoB gene is not a significant determinant of the synthesis of apoB-containing lipoproteins, and by inference, of the regulation of the plasma LDL concentration. Here we report the discovery of a common polymorphism in the promoter region of the apoB gene, a C to T substitution at position -516. The -516T allele is associated with an increase in the basal transcription of the apoB gene (+41%, P < 0.05) in vitro in transfected HepG2 cells. Healthy middle-aged men who are homozygous for the -516T allele have 12% higher plasma LDL cholesterol levels than healthy homozygotes for the -516C allele (P < 0.05). The frequency of the -516T allele is significantly higher in young postinfarction patients (0.38) than in population-based controls (0.30) when the comparison is restricted to subjects without severe hypercholesterolemia who are homozygous for the apoE3 allele (P < 0.05).

It is concluded that variation in the rate of transcription of the apoB gene can affect plasma LDL levels and influences the risk of CHD in middle-aged men.—van 't Hooft, F. M., S. Jormsjö, B. Lundahl, P. Tornvall, P. Eriksson, and A. Hamsten. A functional polymorphism in the apolipoprotein B promoter that influences the level of plasma low density lipoprotein. J. Lipid Res. 1999. 40: 1686;–1694.

Supplementary key words: DNA, cholesterol, restriction fragment length polymorphism, lipoproteins, coronary heart disease

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