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

Apolipoprotein (apo) B is the structural protein moiety of plasma low densi ty lipoprotein (LDL), an important risk factor for coronary heart disease ( CHD), There is evidence that the rate of synthesis of apoB-containing lipop roteins may play an important role in the regulation of plasma LDL levels. However, it is generally thought that transcriptional regulation of the apo B gene is not a significant determinant of the synthesis of apoB-containing lipoproteins, and by inference, of the regulation of the plasma LDL concen tration. Here we report the discovery of a common polymorphism in the promo ter region of the apoB gene, a C to T substitution at position -516, The -5 16T allele is associated with an increase in the basal transcription of re apoB gene (+41%, P < 0.05) in vitro in transfected HepG2 cells. Healthy mid dle-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 p ostinfarction patients (0.38) than in population-based controls (0.30) when the comparison is restricted to subjects without severe hypercholesterolem ia 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 L DL levels and influences the risk of CHD in middle-aged men.