Background and purpose: Thrombomodulin is expressed at the surface of endothelial cells and controls thrombin generation and thrombin-induced platelets and vascular cell activation. Several thrombomodulin gene polymorphisms have been associated with coronary events and brain infarction. In a previous analysis from the Etude du Profil Génétique de l'Infarctus Cérébral (GENIC) study, we found that soluble thrombomodulin (sTM) concentration modulated the risk of and prognosis for brain infarction.
Methods: In 474 brain infarction cases and 483 controls from the GENIC study, we investigated the relationship between three thrombomodulin gene polymorphisms (-1748G/C, -1208/-1209delTT, +1418C/T) and sTM levels, brain infarction risk and 5-year mortality after stroke.
Results: The three polymorphisms were in linkage disequilibrium and defined three major haplotypes with no influence on sTM concentration (all P values > 0.16). Single locus and haplotype analyses found no significant association with brain infarction, even when the analysis was restricted to individuals without a vascular history. After 5 years of follow-up, we found no relationship with vascular or total mortality (all P values > 0.64).
Conclusion: Our results suggest that these three thrombomodulin gene polymorphisms do not contribute to sTM level variations and are not associated with risk of brain infarction and mortality after stroke.