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

Abstract

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.

• Authors: F M van 't Hooft, S Jormsjö, B Lundahl, P Tornvall, P Eriksson, A Hamsten
• Journal: Journal of lipid research (J Lipid Res) Vol. 40 Issue 9 Pg. 1686-94 (Sep 1999) ISSN: 0022-2275 [Print] United States
• PMID: 10484616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins B
• DNA Primers
• Lipoproteins, LDL
• Nuclear Proteins

Topics

• Adult
• Alleles
• Apolipoproteins B (genetics)
• Base Sequence
• Case-Control Studies
• Coronary Disease (blood, etiology, genetics)
• DNA Primers (genetics)
• Humans
• Lipoproteins, LDL (blood)
• Male
• Middle Aged
• Myocardial Infarction (blood, etiology, genetics)
• Nuclear Proteins (metabolism)
• Polymorphism, Genetic
• Promoter Regions, Genetic
• Risk Factors
• Transcription, Genetic