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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1098-1104.)
© 1999 American Heart Association, Inc.

Original Contributions

Mutations in Promoter Region of Thrombomodulin and Venous Thromboembolic Disease

Léna Le Flem; Véronique Picard; Joseph Emmerich; Sophie Gandrille; Jean-Noël Fiessinger; Martine Aiach; Martine Alhenc-Gelas

From the Laboratoire d'Hémostase, Hôpital Broussais—AP-HP and Unité INSERM 428, UFR des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.

Correspondence to Dr Martine Alhenc-Gelas, Laboratoire d'Hémostase, Hôpital Broussais, 96 rue Didot, F-75674 Paris Cedex 14, France. E-mail martine.alhenc-gelas{at}brs.ap-hop-paris.fr

Abstract—The present study was designed to analyze the thrombomodulin proximal promoter region spanning nucleotides -293 to -12 to search for polymorphisms that could modify thrombomodulin gene expression in patients with venous thromboembolic disease. The study population comprised 205 patients and 394 healthy subjects of similar age and sex distribution. No polymorphisms and only 1 point mutation (G-33A) were found. The G-33A mutation was present at the heterozygous state in 2 patients and in 1 control. Being more frequent in the patients (0.97%) than in the controls (0.25%), the G-33A mutation might be a risk factor for venous thrombosis. To investigate the effect of this mutation on the thrombomodulin promoter activity, the proximal promoter region of the gene (bearing or not bearing the G-33A mutation) was inserted into a promotorless expression vector, upstream of the firefly luciferase gene, and transiently transfected into EA.hy926 endothelial cells. Under the conditions of the assay, the G-33A mutation mildly decreased the promoter activity. This study confirms that abnormalities of the thrombomodulin proximal promoter are not frequent in patients with venous thromboembolism.

Key Words: thrombomodulin • thrombosis • coagulation • gene

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