RT Journal Article
T1 Causal Effect of MMP-1 (Matrix Metalloproteinase-1), MMP-8, and MMP-12 Levels on Ischemic Stroke: A Mendelian Randomization Study.
A1 Carcel-Marquez, Jara
A1 Cullell, Natalia
A1 Muiño, Elena
A1 Gallego-Fabrega, Cristina
A1 Lledos, Miquel
A1 Ibañez, Laura
A1 Krupinski, Jerzy
A1 Montaner, Joan
A1 Cruchaga, Carlos
A1 Lee, Jin-Moo
A1 Gill, Dipender
A1 Pare, Guillaume
A1 Mola-Caminal, Marina
A1 Roquer, Jaume
A1 Jimenez-Conde, Jordi
A1 Marti-Fabregas, Joan
A1 Fernandez-Cadenas, Israel
K1 atherosclerosis
K1 ischemic stroke
K1 metalloproteinase
K1 modified Rankin Scale
K1 risk factor
AB 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. 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). 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]; q value=7.43×10−5), and with subtypes of stroke, large-artery atherosclerosis: MMP-1 (odds ratio=0.95 [95% CI, 0.92–0.98]; q value=0.01) and MMP-12 (odds ratio=0.71 [95% CI, 0.65–0.77]; q value=5.11×10−14); small-vessel occlusion: MMP-8 (odds ratio=1.24 [95% CI, 1.06–1.45]; q value=0.03). No associations were found in relation to stroke outcome. 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.
PB Lippincott Williams & Wilkins
YR 2021
FD 2021-04-27
LK http://hdl.handle.net/10668/17637
UL http://hdl.handle.net/10668/17637
LA en
NO Cárcel-Márquez J, Cullell N, Muiño E, Gallego-Fabrega C, Lledós M, Ibañez L, et al. Causal Effect of MMP-1 (Matrix Metalloproteinase-1), MMP-8, and MMP-12 Levels on Ischemic Stroke: A Mendelian Randomization Study. Stroke. 2021 Jul;52(7):e316-e320.
DS RISalud
RD Apr 4, 2025