Carcel-Marquez, JaraCullell, NataliaMuiño, ElenaGallego-Fabrega, CristinaLledos, MiquelIbañez, LauraKrupinski, JerzyMontaner, JoanCruchaga, CarlosLee, Jin-MooGill, DipenderPare, GuillaumeMola-Caminal, MarinaRoquer, JaumeJimenez-Conde, JordiMarti-Fabregas, JoanFernandez-Cadenas, Israel2023-02-092023-02-092021-04-27Cárcel-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.http://hdl.handle.net/10668/17637MMP (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.enatherosclerosisischemic strokemetalloproteinasemodified Rankin Scalerisk factorBiomarkersCohort StudiesFemaleGenome-Wide Association StudyHumansIschemic StrokeMaleMatrix Metalloproteinase 1Matrix Metalloproteinase 12Matrix Metalloproteinase 8Mendelian Randomization Analysisresearch article33902302Restricted AccessMetaloproteinasas de la matrizAccidente cerebrovascular isquémicoAsociaciónPlasmaArteriasIsquemiaAterosclerosisAccidente vascular cerebral lacunarGenomaFactores de riesgo10.1161/STROKEAHA.120.0330411524-4628https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.033041