Causal Effect of MMP-1 (Matrix Metalloproteinase-1), MMP-8, and MMP-12 Levels on Ischemic Stroke Journal Articles uri icon

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  • Background and Purpose:MMP (matrix metalloproteinase) levels have been widely associated with ischemic stroke risk and poststroke outcome. However, their role as a risk factor or as a subeffect because of ischemia is uncertain.Methods:We performed a literature search of genome-wide studies that evaluate serum/plasma levels of MMPs. We used a 2-sample Mendelian randomization approach to evaluate the causality of MMP levels on ischemic stroke risk or poststroke outcome, using 2 cohorts: MEGASTROKE (n=440 328) and GODs (n=1791).Results:Genome-wide association studies of MMP-1, MMP-8, and MMP-12 plasma/serum levels were evaluated. A significant association, which was also robust in the sensitivity analysis, was found with all ischemic strokes: MMP-12 (odds ratio=0.90 [95% CI, 0.86–0.94];qvalue=7.43×105), and with subtypes of stroke, large-artery atherosclerosis: MMP-1 (odds ratio=0.95 [95% CI, 0.92–0.98];qvalue=0.01) and MMP-12 (odds ratio=0.71 [95% CI, 0.65–0.77];qvalue=5.11×1014); small-vessel occlusion: MMP-8 (odds ratio=1.24 [95% CI, 1.06–1.45];qvalue=0.03). No associations were found in relation to stroke outcome.Conclusions:Our study suggests a causal link between lower serum levels of MMP-12 and the risk of ischemic stroke, lower serum levels of MMP-1 and MMP-12 and the risk of large-artery stroke and higher serum levels of MMP-8 and the risk of lacunar stroke.


  • Cárcel-Márquez, Jara
  • Cullell, Natalia
  • Muiño, Elena
  • Gallego-Fabrega, Cristina
  • Lledós, Miquel
  • Ibañez, Laura
  • Krupinski, Jerzy
  • Montaner, Joan
  • Cruchaga, Carlos
  • Lee, Jin-Moo
  • Gill, Dipender
  • Pare, Guillaume
  • Mola-Caminal, Marina
  • Roquer, Jaume
  • Jimenez-Conde, Jordi
  • Martí-Fàbregas, Joan
  • Fernandez-Cadenas, Israel

publication date

  • July 2021

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