Thrombomodulin gene polymorphisms in brain infarction and mortality after stroke

Background 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 Genetique de l'Infarctus Cerebral (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.