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 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.
Robinet
Peggy
P
Laboratoire de Biochimie Appliquée, UFR de pharmacie, Châtenay-Malabry, France.
Védie
Benoit
B
Chironi
Gilles
G
Gariépy
Jérôme
J
Simon
Alain
A
Moatti
Nicole
N
Paul
Jean Louis
JL
D000328:Adult; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005263:Femoral Artery / Q000000981:diagnostic imaging; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics; D006973:Hypertension / Q000235:genetics; D002537:Intracranial Arteriosclerosis / Q000235:genetics*; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012907:Smoking / Q000235:genetics; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics*; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
D004268:DNA-Binding Proteins; D008055:Lipids; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors