AI Article Synopsis
- MMPs and TIMPs play a role in the effectiveness of rtPA therapy for patients with acute ischemic stroke (AIS) and can also influence recovery and adverse effects.
- The study aimed to investigate whether specific genetic variations in the MMP-2, MMP-9, and TIMP-2 genes affect the response to rtPA treatment and the occurrence of side effects in AIS patients.
- Findings indicated no direct link between these genetic variations and therapy outcomes, but the TT genotype of the MMP-9-1562C/T polymorphism was associated with increased risk of serious complications like intracranial hemorrhage following rtPA treatment.
Article 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 regard 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, was 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.
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| http://dx.doi.org/10.1002/phar.2532 | DOI Listing |
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