Characterization of polymorphic structure of SREBP-2 gene: role in atherosclerosis

Sterol regulatory element binding proteins (SREBPs) are membrane-bound transcription factors that control the metabolism of cholesterol and fatty acids in mammalian cells. We postulated that polymorphisms (SNPs) in SREBP-2 gene might influence lipid parameters and the risk of coronary atherosclerosi...

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Bibliographic Details
Published in:Atherosclerosis 2003-06, Vol.168 (2), p.381-387
Main Authors: Robinet, Peggy, Védie, Benoit, Chironi, Gilles, Gariépy, Jérôme, Simon, Alain, Moatti, Nicole, Paul, Jean-Louis
Format: Article
Language:English
Subjects:
Adult
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Carotid Arteries - diagnostic imaging
Carotid Artery Diseases - genetics
DNA-Binding Proteins - genetics
Femoral Artery - diagnostic imaging
Gene Frequency
Genotype
Humans
Hypercholesterolemia - genetics
Hypertension - genetics
IMT
Intracranial Arteriosclerosis - genetics
Linkage Disequilibrium
Lipids - blood
Medical sciences
Middle Aged
Polymerase Chain Reaction
Polymorphism
Polymorphism, Single Nucleotide
Polymorphism, Single-Stranded Conformational
Smoking - genetics
SREBP-2
Sterol Regulatory Element Binding Protein 2
Transcription Factors - genetics
Tunica Intima - diagnostic imaging
Tunica Media - diagnostic imaging
Ultrasonography
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Summary:Sterol regulatory element binding proteins (SREBPs) are membrane-bound transcription factors that control the metabolism of cholesterol and fatty acids in mammalian cells. We postulated that polymorphisms (SNPs) in SREBP-2 gene might influence lipid parameters and the risk of coronary atherosclerosis. PCR-SSCP analysis and direct sequencing of DNA from 64 asymptomatic hypercholesterolemic men revealed seven genetic SREBP-2 SNPs. The genotype distribution of four of these SNPs (1668G>T, 1784G>C, 3474T>C and 3705C>T), and their influence on plasma lipid values and clinical parameters was studied in 655 asymptomatic men previously selected for the presence of at least one cardiovascular risk factor (hypertension, hypercholesterolemia, tobacco consumption). No significant relation was found with lipid parameters but there was a significant association between the 1784G>C polymorphism and intima-media thickness (IMT) measured in 497 subjects. Thus, a common variation in the SREBP-2 gene is related with early-stage carotid atherosclerosis in subjects with a risk of cardiovascular events without detectable change in plasma lipid levels.
ISSN:0021-9150
1879-1484
DOI:10.1016/S0021-9150(03)00144-8