The Impact of Genetically Proxied AMPK Activation, the Target of Metformin, on Functional Outcome Following Ischemic Stroke / 대한뇌졸중학회지
Journal of Stroke
; : 266-271, 2023.
Article
em En
| WPRIM
| ID: wpr-1001575
Biblioteca responsável:
WPRO
ABSTRACT
Background@#and Purpose We performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of genetically proxied AMP-activated protein kinase (AMPK) activation, which is the target of metformin, on functional outcome following ischemic stroke onset. @*Methods@#A total of 44 AMPK-related variants associated with HbA1c (%) were used as instruments for AMPK activation. The primary outcome was the modified Rankin Scale (mRS) score at 3 months following the onset of ischemic stroke, evaluated as a dichotomous variable (3–6 vs. 0–2) and subsequently as an ordinal variable. Summary-level data for the 3-month mRS were obtained from the Genetics of Ischemic Stroke Functional Outcome network, including 6,165 patients with ischemic stroke. The inverse-variance weighted method was used to obtain causal estimates. The alternative MR methods were used for sensitivity analysis. @*Results@#Genetically predicted AMPK activation was significantly associated with lower odds of poor functional outcome (mRS 3–6 vs. 0–2, odds ratio [OR]: 0.06, 95% confidence interval [CI]: 0.01–0.49, P=0.009). This association was maintained when 3-month mRS was analyzed as an ordinal variable. Similar results were observed in the sensitivity analyses, and there was no evidence of pleiotropy. @*Conclusion@#This MR study provided evidence that AMPK activation by metformin may exert beneficial effects on functional outcome following ischemic stroke.
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Índice:
WPRIM
Idioma:
En
Revista:
Journal of Stroke
Ano de publicação:
2023
Tipo de documento:
Article