Safety profile of tissue plasminogen activator treatment among stroke patients carrying a common polymorphism (C-1562T) in the promoter region of the matrix metalloproteinase-9 gene

Background and Purpose - Matrix metalloproteinase- 9 ( MMP- 9) expression, related to blood- brain barrier disruption, has been implicated in the appearance of hemorrhagic transformation ( HT) after tissue plasminogen activator ( tPA) treatment in stroke patients. Because an in vitro functional polymorphism of the promoter region of MMP- 9 gene ( C- 1562T) has been described, we hypothesize that patients carrying this mutation might have higher MMP- 9 levels and greater susceptibility to developing HT when receiving tPA. Methods - We studied strokes involving the middle cerebral artery territory of 61 patients who received tPA < 3 hours after stroke onset. Blood samples were obtained before tPA administration. Plasmatic MMP- 9 determinations were performed ( enzyme- linked immunosorbent assay, ng/ mL), and C- 1562T genotype was determined by polymerase chain reaction. Healthy age- matched control subjects were used to study allele distribution ( n = 59). Hemorrhagic events were classified according to CT criteria ( petechial hemorrhagic infarctions [ HI, 1 to 2] and large parenchymal hemorrhages [ PH, 1 to 2]). Results - Allele distribution was similar in patients and control subjects ( CC/ CT/ TT: 72.3/ 27.7/ 0% versus 79.7/ 20.3/ 0%, respectively; P = 0.37). Among patients, mutation carriers ( CT/ TT alleles) had similar rates of HT and PH than noncarriers ( HT: 23.1% versus 38.2%, P = 0.49; PH: 15.4% versus 17.6%, P = 1.0). Although the highest MMP- 9 level corresponded to patients who later developed a PH ( PH, 191.4 ng/ mL; non- PH, 68.05 ng/ mL; P = 0.022), no relation between MMP- 9 mutation presence and plasmatic levels was found ( CC, 127.12 ng/ mL; CT/ TT, 46.31 ng/ mL; P = 0.11). Conclusions - Although MMP- 9 level predicts PH appearance after tPA treatment, no relationship exists with the C- 1562T polymorphism, probably because this mutation is not functional in response to cerebral ischemia in vivo.