Genetically Determined Plasma Hepatocyte Growth Factor Levels Are Associated With the Risk and Prognosis of Ischemic Stroke.
Stroke
; 55(6): 1535-1542, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38572663
ABSTRACT
BACKGROUND:
Observational studies suggest that hepatocyte growth factor (HGF) is associated with the risk and prognosis of ischemic stroke, but the causality of these associations remains unclear. Therefore, we conducted Mendelian randomization (MR) analyses to explore the associations of genetically determined plasma HGF levels with the risk and prognosis of ischemic stroke.METHODS:
A total of 13 single-nucleotide polymorphisms associated with plasma HGF were selected as genetic instruments based on the data from a genome-wide association study with 21â 758 European participants. Summary data about the risk of ischemic stroke were obtained from the MEGASTROKE (Multiancestry Genome-Wide Association Study of Stroke) Consortium with 34â 217 ischemic stroke cases and 406â 111 controls of European ancestry, and summary data about the prognosis of ischemic stroke were obtained from the GISCOME study (Genetics of Ischaemic Stroke Functional Outcome) with 6165 European patients with ischemic stroke. We conducted an inverse-variance weighted Mendelian randomization analysis followed by a series of sensitivity analyses to evaluate the associations of genetically determined plasma HGF with the risk and prognosis of ischemic stroke.RESULTS:
The primary analyses showed that genetically determined high HGF was associated with an increased risk of ischemic stroke (odds ratio per SD increase, 1.11 [95% CI, 1.04-1.19]; P=1.10×10-3) and poor prognosis of ischemic stroke (odds ratio per SD increase, 2.43 [95% CI, 1.76-3.52]; P=6.35×10-8). In the secondary analysis, genetically determined plasma HGF was associated with a high risk of large atherosclerotic stroke (odds ratio per SD increase, 1.39 [95% CI, 1.18-1.63]; P=5.08×10-5) but not small vessel stroke and cardioembolic stroke. Mendelian randomization-Egger regression showed no directional pleiotropy for all associations, and the sensitivity analyses with different Mendelian randomization methods further confirmed these findings.CONCLUSIONS:
We found positive associations of genetically determined plasma HGF with the risk and prognosis of ischemic stroke, suggesting that HGF might be implicated in the occurrence and development of ischemic stroke.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento de Hepatócito
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Polimorfismo de Nucleotídeo Único
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Estudo de Associação Genômica Ampla
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Análise da Randomização Mendeliana
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AVC Isquêmico
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article