Thrombomodulin gene polymorphisms in brain infarction and mortality after stroke.
OBJECTIVE
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).


CONCLUSIONS
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.
Olivot
Jean-Marc
JM
INSERM U698 and Denis Diderot University - Paris VII, Dept. of Neurology and Stroke Center, Bichat University Hospital, Paris, France.
Labreuche
Julien
J
De Broucker
Thomas
T
Poirier
Odette
O
Cambien
François
F
Aiach
Martine
M
Amarenco
Pierre
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020520:Brain Infarction / Q000235:genetics* / Q000401:mortality*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D018180:Thrombomodulin / Q000235:genetics*; D013997:Time Factors
D018180:Thrombomodulin