Identification of two polymorphisms in the early growth response protein-1 gene: possible association with lipid variables

被引:12
作者
Brand, E
Herrmann, SM
Nicaud, V
Evans, A
Ruidavets, JB
Arveiler, D
Luc, G
Cambien, F
Soubrier, F
机构
[1] INSERM, U525, F-75005 Paris, France
[2] MONICA Project, Belfast, Antrim, North Ireland
[3] MONICA Project, Toulouse, France
[4] MONICA Project, Strasbourg, France
[5] MONICA Project, Lille, France
[6] Hop St Louis, INSERM, U525, F-75475 Paris 10, France
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2000年 / 78卷 / 02期
关键词
early growth response factor-1; C-151T polymorphism; transcription factor; lipid variables; myocardial infarction;
D O I
10.1007/s001090000074
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Early growth response factor (EGR)-1 may play an important role in the development of atherosclerosis by inducing the expression of several relevant genes which contribute to the complex modulation of vascular structure and function, leading to vascular occlusive lesions. To investigate the possible role of molecular variants in the human EGR-1 gene for the predisposition to atherosclerosis or coronary heart disease we screened the 5'- and 3'- flanking regions and the entire coding sequence for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism analysis and sequencing. Male patients (n=615) with myocardial infarction and 720 age-matched, male control subjects of the Etude Cas-Temoin de l'Infarctus du Myocarde were genotyped for two newly identified polymorphisms in the 5'- (C-151T) and 3'- (T+861C) flanking region of the EGR-1 gene using hybridization with allele-specific oligonucleotides. Allele and genotype frequencies did not significantly differ between patients with myocardial infarction and control subjects without coronary heart disease. In controls not taking hypolipidemic drugs there was a significant association of the -151T allele with lower plasma levels of total cholesterol (P=0.029), low-density lipoprotein cholesterol (P=0.025) and apolipoprotein B (P=0.038) and a higher ratio of high-density to low-density lipoprotein (P=0.049) than with the C-151 allele. We conclude that the C-151T polymorphism of the EGR-1 gene may contribute to modifications of the lipid metabolism. Om findings need to be replicated in independent studies, and in vitro promoter studies should evaluate the functional consequence of the -151T allele, which disrupts a consensus core sequence for the ubiquitous transcription factor activator protein 4.
引用
收藏
页码:81 / 86
页数:6
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