TT genotype of the MMP-9-1562C/T polymorphism may be a risk factor for thrombolytic therapy-induced hemorrhagic complications after acute ischemic stroke.
acute ischemic stroke
matrix metalloproteinases
pharmacogenetics
polymorphisms
rtPA
thrombolytic therapy
Journal
Pharmacotherapy
ISSN: 1875-9114
Titre abrégé: Pharmacotherapy
Pays: United States
ID NLM: 8111305
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
10
04
2021
received:
14
02
2021
accepted:
10
04
2021
pubmed:
5
5
2021
medline:
7
1
2022
entrez:
4
5
2021
Statut:
ppublish
Résumé
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. 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. 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. 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). TT genotype of the MMP-9-1562C/T polymorphism may be a risk factor for rtPA-induced hemorrhagic complications after AIS.
Substances chimiques
Tissue Inhibitor of Metalloproteinase-2
127497-59-0
Tissue Plasminogen Activator
EC 3.4.21.68
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
562-571Informations de copyright
© 2021 Pharmacotherapy Publications, Inc.
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