DOI: 10.1097/wnf.0000000000000710 ISSN: 0362-5664

Extracellular Matrix Remodeling Gene Polymorphisms and Adverse Effects of Thrombolytic Therapy in Acute Ischemic Stroke

Marija Dusanovic Pjevic, Lena Sarenac, Katarina Samardzic, Biljana Jekic, Milica Rasic, Tatjana Damnjanovic, Nela Maksimovic, Dijana Perovic, Milica Pesic, Ljubica Vojvodic, Jelena Trickovic, Ana Djuranovic Uklein, Milka Grk
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Objectives:

Thrombolytic therapy with Alteplase is the standard treatment for eligible patients with acute ischemic stroke, but clinical response and hemorrhagic complications vary considerably among patients. This study aimed to investigate whether selected polymorphisms within the MMP-8 and MMP-9 genes are associated with baseline stroke severity, functional recovery, and hemorrhagic complications after thrombolytic therapy.

Materials and Methods:

Over a 24-month period, 166 Caucasian patients with acute ischemic stroke treated with intravenous Alteplase were prospectively enrolled. Genotyping was performed for MMP-9 rs3918241 and rs3918249, and MMP-8 rs1940475 and rs11225395 polymorphisms. Associations with neurological severity, functional outcome, and postthrombolytic hemorrhagic complications were analyzed. Haplotype analysis was performed for the investigated MMP-8 and MMP-9 variants.

Results:

No significant associations were observed between the investigated MMP-9 polymorphisms and functional recovery or hemorrhagic complications after Alteplase treatment. However, carriers of the MMP-9 rs3918249 T allele had lower National Institutes of Health Stroke Scale scores at admission, suggesting a less severe initial clinical presentation. For MMP-8 , patients who developed symptomatic intracerebral hemorrhage were significantly more likely to carry the rs1940475 TT genotype ( P = 0.032; odds ratio = 5.10; 95% CI: 1.27-20.56). Haplotype analysis showed strong linkage disequilibrium between rs1940475 and rs11225395, and the TG haplotype was significantly more frequent in patients without hemorrhagic transformation than in those with hemorrhagic transformation.

Conclusions:

The investigated MMP-9 polymorphisms were not associated with postthrombolytic recovery or hemorrhagic complications. In contrast, MMP-8 rs1940475 and MMP-8 haplotypes may be related to hemorrhagic risk after Alteplase therapy.

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