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 Ͻ 0.05) in vitro in transfected HepG2 cells. Healthy middle-aged men who are homozygous for the Ϫ 516T allele have 12% higher plasma LDL cholesterol levels than healthy homozygotes for the ؊ 516C allele ( P Ͻ 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 Ͻ 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.

Effect of APOB gene polymorphisms on body mass index, blood pressure, and total cholesterol levels: A cross-sectional study in Mexican population

“…Individuals carrying T allele had lower BMI values than those with C allele. This variant is located in the promoter region and it has been reported that T allele induces a significant increase in the transcription of APOB gene [ 31 ] ; and consequently, in both an increased very low-density lipoproteins secretion and a greater availability of fatty acids, which could be stored in adipocytes, thus favoring a rise in the BMI. Nevertheless, this is contrary to what was observed in the present study, therefore, in order to know the relationship between T allele and the reduction of BMI, further studies are required.…”

Clinical Value Distribution of Polymorphism of the Lipidtransport Systems Genes in Patients With Unstable Angina and Coronary Heart Disease in Family History

“…Полиморфизм генов, регулирующих транспорт и метаболизм липидов -аполипопротеинов А, В и Е играет важную роль в липидном метаболизме и непосредственно может влиять на развитие атеросклероза. Белки аполипопротеинов А, В и Е участвуют в создании, секреции, транспорте и связывании макромолекулярных липопротеидных комплексов [1,2,3].…”