2,5TT genotype of the MMP‐9‐1562C/T polymorphism may be a risk factor for thrombolytic therapy‐induced hemorrhagic complications after acute ischemic stroke
【Abstract】 Introduction Levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) influence recombinant tissue plasminogen activator (rtPA) therapy response in patients with acute ischemic stroke (AIS). Serum levels of MMPs and TIMPs along with the expression of genes coding these proteins are related to the recovery and appearance of adverse effects (AE) after AIS. Consequently, it is important to explore whether polymorphisms in regulatory sequences of MMPs and TIMPs are associated with rtPA response in AIS patients. Objectives To determine whether selected polymorphic variants within MMP‐2, MMP‐9, and TIMP‐2 genes may influence rtPA therapy response with regards to outcomes in patients with AIS and the occurrence of AE. Methods Our study included 166 patients suffering AIS, treated with rtPA. Patients’ recovery was estimated using the Modified Rankin Scale (mRS) 3 months after the AIS occurred. Favorable outcome was defined with scores 0‐1, and poor outcome with scores 2‐6. Genotyping was performed using Real‐Time PCR (rs243866, rs243865, rs243864, rs2277698, and rs8179090) and PCR‐RFLP (rs2285053, rs3918242) methods. Additionally, rtPA AE were followed during the hospitalization. Results There was no significant association between genotypes and alleles of selected polymorphisms and rtPA therapy response measured through the decrease of the mRS score in patients with AIS. Intracranial hemorrhage, as well as parenchymal hematoma type 2, were significantly more frequent in patients with TT genotype of the MMP‐9‐1562C/T polymorphism (p=0.047, p=0.011, respectively). Patients with intracranial hemorrhages after rtPA were significantly more likely to have the TT genotype of TIMP‐2‐303C/T polymorphism and the TT genotype of MMP‐9‐1562C/T polymorphism (p<0.001). Conclusion TT genotype of the MMP‐9‐1562C/T polymorphism may be a risk factor for rtPA‐induced hemorrhagic complications after AIS.
【Author】 Marija Dusanovic Pjevic, Biljana Jekic, Ljiljana Beslac Bumbasirevic, Ljubica Vojvodic, Tatjana Damnjanovic, Milka Grk, Nela Maksimovic, Milica Pesic, Milica Gulic, Jelena Trickovic, Katarina Kacar
【Keywords】 acute ischemic stroke, rtPA, thrombolytic therapy, pharmacogenetics, matrix metalloproteinases, polymorphisms
【Journal】 Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy(IF：1) Time：2021-05-04