Mutations in Promoter Region of Thrombomodulin and Venous Thromboembolic Disease

Arteriosclerosis, Thrombosis, and Vascular Biology - Tập 19 Số 4 - Trang 1098-1104 - 1999
Léna Le Flem1, Véronique Picard1, Joseph Emmerich1, Sophie Gandrille1, Jean‐Noël Fiessinger1, Martine Aiach1, Martine Alhenc‐Gelas1
1From the Laboratoire d’Hémostase, Hôpital Broussais—AP-HP and Unité INSERM 428, UFR des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.

Tóm tắt

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.

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Arteriosclerosis, Thrombosis, and Vascular Biology

Tập 19 Số 4

1098-1104

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