title: 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.affiliation: Atherosclerosis Research Unit, King Gustaf V Research Institute, and Department of Medicine, Karolinska Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden.
authors.forename: F M
authors.initials: FM
authors.lastname: van 't Hooft
authors.forename: S
authors.initials: S
authors.lastname: Jormsjö
authors.forename: B
authors.initials: B
authors.lastname: Lundahl
authors.forename: P
authors.initials: P
authors.lastname: Tornvall
authors.forename: P
authors.initials: P
authors.lastname: Eriksson
authors.forename: A
authors.initials: A
authors.lastname: Hamsten
mesh_terms: D000328:Adult; D000483:Alleles; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000209:etiology / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014158:Transcription, Genetic
chemical_list: D001055:Apolipoproteins B; D017931:DNA Primers; D008077:Lipoproteins, LDL; D009687:Nuclear Proteins