The present study was designed to analyze the thrombomodulin proximal promo
ter region spanning nucleotides - 293 to -12 to search for polymorphisms th
at could modify thrombomodulin gene expression in patients with venous thro
mboembolic disease. The study population comprised 205 patients and 394 hea
lthy subjects of similar age and sex distribution. No polymorphisms and onl
y I point mutation (G-33A) were found. The G-33A mutation was present at th
e heterozygous state in 2 patients and in 1 control. Being more frequent in
the patients (0.97%) than in the controls (0.25%), the C-33A mutation migh
t be a risk factor for venous thrombosis. To investigate the effect of this
mutation on the thrombomodulin promoter activity, the proximal promoter re
gion of the gene (bearing or not bearing the G-33A mutation) was inserted i
nto a promotorless expression vector, upstream of the firefly luciferase ge
ne, and transiently transfected into EA.hy926 endothelial cells. Under the
conditions of the assay, the C-33A mutation mildly decreased the promoter a
ctivity. This study confirms that abnormalities of the thrombomodulin proxi
mal promoter are not frequent in patients with Venous thromboembolism.