Causal Effect of MMP-1 (Matrix Metalloproteinase-1), MMP-8, and MMP-12 Levels on Ischemic Stroke: A Mendelian Randomization Study.
Stroke
; 52(7): e316-e320, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33902302
ABSTRACT
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, 0.860.94]; q value=7.43×10−5), and with subtypes of stroke, large-artery atherosclerosis MMP-1 (odds ratio=0.95 [95% CI, 0.920.98]; q value=0.01) and MMP-12 (odds ratio=0.71 [95% CI, 0.650.77]; q value=5.11×10−14); small-vessel occlusion MMP-8 (odds ratio=1.24 [95% CI, 1.061.45]; 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metaloproteinase 1 da Matriz
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Metaloproteinase 8 da Matriz
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Metaloproteinase 12 da Matriz
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Estudo de Associação Genômica Ampla
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Análise da Randomização Mendeliana
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AVC Isquêmico
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article