ACE gene polymorphisms influence t-PA-induced brain vessel reopening following ischemic stroke.
Angiotensin converting enzyme (ACE) influences vessels tone and the coagulation/fibrinolysis system. The ACE gene I/D polymorphism has been linked with PAI-1 and fibrinogen levels and with Factors VII and X activities. Therefore, we aimed to test whether I/D polymorphism could be related to thrombolysis safety and efficacy. We studied strokes involving the middle cerebral artery (MCA) territory of patients who received t-PA <3 h of stroke onset. Blood samples were obtained before t-PA administration to measure fibrinogen, PAI-1, Factors VII and X. I/D polymorphism was determined by polymerase chain reaction and agarose electrophoresis. Recanalization rates were serially evaluated by Transcranial Doppler. Among 96 included patients the genotype frequency was: DD=33.3%, ID=57.3% and II=9.4%. A strong association was found between DD homozygous and successful recanalization rates (DD=69.2%, ID+II=31.6%, p=0.002 at 1 h; DD=91.3%, ID+II=51%, p=0.001 at 6 h; DD=100%, ID+II=72.3%, p=0.003 at 24 h post-t-PA administration). In fact, DD genotype was an independent predictor of recanalization (OR=4.3 95% CI 1.35-13.49, p=0.013). No relation was found between I/D polymorphism and symptomatic hemorrhagic complications (p=0.237). No association between ACE genotypes and Factor VII or Factor X activities, neither with fibrinogen or PAI-1 levels was observed. DD homozygous is strongly associated with MCA recanalization following t-PA treatment. Mechanisms of benefit remain unknown since I/D polymorphism had similar FVII and X activities and PAI-1 and fibrinogen levels in our stroke population.
Fernández-Cadenas
Israel
I
Neurovascular Research Laboratory and Neurovascular Unit, Departamento de Medicina Interna Universitat Autonoma de Barcelona, Edifici de Recerca, Vall d'Hebron Hospital, Pg Vall d'Hebron 119-129, 08035, Barcelona, Spain.
Molina
Carlos Alberto
CA
Alvarez-Sabín
José
J
Ribó
Marc
M
Penalba
Anna
A
Ortega-Torres
Laura
L
Delgado
Pilar
P
Quintana
Manolo
M
Rosell
Anna
A
Montaner
Joan
J
D000208:Acute Disease; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D005167:Factor VII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D009126:Muscle Relaxation; D016254:Mutagenesis, Insertional; D011110:Polymorphism, Genetic; D012083:Renin / Q000235:genetics*; D017384:Sequence Deletion; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D005167:Factor VII; D005170:Factor X; D010959:Tissue Plasminogen Activator; D012083:Renin