TY - JOUR
T1 - Causal Effect of MMP-1 (Matrix Metalloproteinase-1), MMP-8, and MMP-12 Levels on Ischemic Stroke
T2 - A Mendelian Randomization Study
AU - Cárcel-Márquez, Jara
AU - Cullell, Natalia
AU - Muiño, Elena
AU - Gallego-Fabrega, Cristina
AU - Lledós, Miquel
AU - Ibañez, Laura
AU - Krupinski, Jerzy
AU - Montaner, Joan
AU - Cruchaga, Carlos
AU - Lee, Jin Moo
AU - Gill, Dipender
AU - Paré, Guillaume
AU - Mola-Caminal, Marina
AU - Roquer, Jaume
AU - Jimenez-Conde, Jordi
AU - Martí-Fàbregas, Joan
AU - Fernandez-Cadenas, Israel
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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]; 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. 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.
AB - 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]; 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. 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.
KW - atherosclerosis
KW - ischemic stroke
KW - metalloproteinase
KW - modified Rankin Scale
KW - risk factor
UR - http://www.scopus.com/inward/record.url?scp=85108959701&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.120.033041
DO - 10.1161/STROKEAHA.120.033041
M3 - Article
C2 - 33902302
AN - SCOPUS:85108959701
SN - 0039-2499
VL - 52
SP - E316-E320
JO - Stroke
JF - Stroke
IS - 7
ER -