Open AccessPolymorphisms in the 5′ Regulatory Region of the Tissue Factor Gene and the Risk of Myocardial Infarction and Venous Thromboembolism
Author(s) -
Emmanuel Arnaud,
Véronique Barbalat,
Viviane Nicaud,
François Cambien,
Alun Evans,
Caroline Morrison,
Dominique Arveiler,
Gérald Luc,
JeanBernard Ruidavets,
Joseph Emmerich,
JeanNoël Fiessinger,
Martine Aiach
Publication year - 2000
Publication title -
arteriosclerosis, thrombosis, and vascular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.007
H-Index - 270
eISSN - 1524-4636
pISSN - 1079-5642
DOI - 10.1161/01.atv.20.3.892
Subject(s) - tissue factor , haplotype , myocardial infarction , allele , thrombus , thrombosis , odds ratio , medicine , venous thrombosis , single nucleotide polymorphism , coronary thrombosis , risk factor , genotyping , case control study , cardiology , coagulation , gene , genetics , biology , genotype
—Tissue factor (TF) is a transmembrane protein considered to be responsible for the initiation of coagulation. TF gene expression may be induced in monocytes and endothelial cells and is present in atherosclerotic plaque to initiate thrombus formation. To investigate whether individual differences in TF gene expression could predispose subjects to thrombosis, we sequenced the 5′ domain of the gene up to nucleotide 2732 and found 6 different polymorphisms: 4 of them were completely concordant and defined 2 haplotypes with similar frequencies, designated as 1208 D and 1208 I. Genotyping of patients with myocardial infarction in a case-control study involving 2354 subjects showed no association between the polymorphisms and nonfatal coronary thrombosis. In another study involving 255 patients with venous thromboembolism and 1204 controls, alleleD was less common in the cases (P =0.022). The odds ratio associated with the presence of at least 1D allele was 0.72 (P =0.031). Comparison of subgroups of control subjects who were homozygous for theD orI allele demonstrated a lower plasma TF concentration inDD homozygotes. These results indicate that the TF gene promoter exists in 2 major forms differing at 4 sites. The 1208 D haplotype is not associated with coronary thrombosis but is associated with reduced plasma TF levels and a lower risk of venous thrombosis.