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

被引:36
作者
Robinet, P
Védie, B
Chironi, G
Gariépy, K
Simon, A
Moatti, N
Paul, JL
机构
[1] Hop Europeen Georges Pompidou, Serv Biochim Cardiovasc, F-75908 Paris 15, France
[2] UFR Pharm, Lab Biochim Appl, Chatenay Malabry, France
[3] Hop Broussais, INSERM, U28, Paris, France
[4] Hop Broussais, Ctr Med Pevent Cardiovasc, Paris, France
关键词
atherosclerosis; IMT; polymorphism; SREBP-2;
D O I
10.1016/S0021-9150(03)00144-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:381 / 387
页数:7
相关论文
共 26 条
[1]  
ASSMANN G, 1983, CLIN CHEM, V29, P2026
[2]   Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterol [J].
Bist, A ;
Fielding, PE ;
Fielding, CJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10693-10698
[3]   Relation of intima-media thickness to atherosclerotic plaques in carotid arteries - The vascular aging (EVA) study [J].
BonithonKopp, C ;
Touboul, PJ ;
Berr, C ;
Leroux, C ;
Mainard, F ;
Courbon, D ;
Ducimetiere, P .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (02) :310-316
[4]   The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor [J].
Brown, MS ;
Goldstein, JL .
CELL, 1997, 89 (03) :331-340
[5]   Sequence diversity in 36 candidate genes for cardiovascular disorders [J].
Cambien, F ;
Poirier, O ;
Nicaud, V ;
Herrmann, SM ;
Mallet, C ;
Ricard, S ;
Behague, I ;
Hallet, V ;
Blanc, H ;
Loukaci, V ;
Thillet, J ;
Evans, A ;
Ruidavets, JB ;
Arveiler, D ;
Luc, G ;
Tiret, L .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (01) :183-191
[6]   Sex and topographic differences in associations between large-artery wall thickness and coronary risk profile in a French working cohort -: The AXA Study [J].
Gariepy, J ;
Salomon, J ;
Denarié, N ;
Laskri, F ;
Mégnien, JL ;
Levenson, J ;
Simon, A .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (04) :584-590
[7]   RISK-FACTORS AND EARLY EXTRACORONARY ATHEROSCLEROTIC PLAQUES DETECTED BY 3-SITE ULTRASOUND IMAGING IN HYPERCHOLESTEROLEMIC MEN [J].
GIRAL, P ;
PITHOISMERLI, I ;
FILITTI, V ;
LEVENSON, J ;
PLAINFOSSE, MC ;
MAINARDI, C ;
SIMON, AC .
ARCHIVES OF INTERNAL MEDICINE, 1991, 151 (05) :950-956
[8]  
Hayashi K, 1991, PCR Methods Appl, V1, P34
[9]   Disruption of LDL receptor gene in transgenic SREBP-1a mice unmasks hyperlipidemia resulting from production of lipid-rich VLDL [J].
Horton, JD ;
Shimano, H ;
Hamilton, RL ;
Brown, MS ;
Goldstein, JL .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (07) :1067-1076
[10]   SREBP-2, A 2ND BASIC-HELIX-LOOP-HELIX-LEUCINE ZIPPER PROTEIN THAT STIMULATES TRANSCRIPTION BY BINDING TO A STEROL REGULATORY ELEMENT [J].
HUA, XX ;
YOKOYAMA, C ;
WU, J ;
BRIGGS, MR ;
BROWN, MS ;
GOLDSTEIN, JL ;
WANG, XD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (24) :11603-11607