This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arnaud, E. Articles by Aiach, M. Search for Related Content PubMed PubMed Citation Articles by Arnaud, E. Articles by Aiach, M. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Deep Vein Thrombosis Heart Attack Related Collections Risk Factors Acute myocardial infarction Epidemiology Coagulation and fibronolysis Genetics of cardiovascular disease

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:892.)
© 2000 American Heart Association, Inc.

Thrombosis

Polymorphisms in the 5' Regulatory Region of the Tissue Factor Gene and the Risk of Myocardial Infarction and Venous Thromboembolism

The ECTIM and PATHROS Studies

Emmanuel Arnaud; Véronique Barbalat; Viviane Nicaud; François Cambien; Alun Evans; Caroline Morrison; Dominique Arveiler; Gérald Luc; Jean-Bernard Ruidavets; Joseph Emmerich; Jean-Noël Fiessinger; Martine Aiach

From Laboratoire d’Hémostase and Service des Maladies Vasculaires, Hôpital Broussais—AP-HP, and Unité INSERM 428, Faculté de Pharmacie, Université René Descartes, Paris (E.A., J.E., J.-N.F., M.A.); Société bioMérieux, Marcy-l’Etoile (V.B.); and Unité INSERM 525, Paris (V.N., F.C.), France; and the MONICA Project: Belfast, Northern Ireland, UK (A.E.); Glasgow, Scotland, UK (C.M.); and Strasbourg (D.A.), Lille (G.L.), and Toulouse (J.-B.R.), France.

Correspondence to Dr Emmanuel Arnaud, Laboratoire d’Hémostase, Hôpital Broussais, 96 rue Didot, F-75674 Paris Cedex 14, France. E-mail emmanuel.arnaud{at}brs.ap-hop-paris.fr

Abstract—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, allele D was less common in the cases (P=0.022). The odds ratio associated with the presence of at least 1 D allele was 0.72 (P=0.031). Comparison of subgroups of control subjects who were homozygous for the D or I allele demonstrated a lower plasma TF concentration in DD 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.

Key Words: tissue factor • gene polymorphisms • venous thromboembolism • myocardial infarction

This article has been cited by other articles:

				P. V. Giannoudis, M. van Griensven, E. Tsiridis, and H. C. Pape The genetic predisposition to adverse outcome after trauma J Bone Joint Surg Br, October 1, 2007; 89-B(10): 1273 - 1279. [Abstract] [Full Text] [PDF]

				N. L. Smith, L. A. Hindorff, S. R. Heckbert, R. N. Lemaitre, K. D. Marciante, K. Rice, T. Lumley, J. C. Bis, K. L. Wiggins, F. R. Rosendaal, et al. Association of Genetic Variations With Nonfatal Venous Thrombosis in Postmenopausal Women JAMA, February 7, 2007; 297(5): 489 - 498. [Abstract] [Full Text] [PDF]

				G. Campo, M. Valgimigli, P. Ferraresi, P. Malagutti, M. Baroni, C. Arcozzi, D. Gemmati, G. Percoco, G. Parrinello, R. Ferrari, et al. Tissue Factor and Coagulation Factor VII Levels During Acute Myocardial Infarction: Association With Genotype and Adverse Events Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2800 - 2806. [Abstract] [Full Text] [PDF]

				A. Malarstig, T. Tenno, N. Johnston, B. Lagerqvist, T. Axelsson, A.-C. Syvanen, L. Wallentin, and A. Siegbahn Genetic Variations in the Tissue Factor Gene Are Associated With Clinical Outcome in Acute Coronary Syndrome and Expression Levels in Human Monocytes Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2667 - 2672. [Abstract] [Full Text] [PDF]

				S.-M. Herrmann, H. Funke-Kaiser, K. Schmidt-Petersen, V. Nicaud, M. Gautier-Bertrand, A. Evans, F. Kee, D. Arveiler, C. Morrison, H.-D. Orzechowski, et al. Characterization of Polymorphic Structure of Cathepsin G Gene: Role in Cardiovascular and Cerebrovascular Diseases Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1538 - 1543. [Abstract] [Full Text] [PDF]