Exploring causal association between circulating inflammatory cytokines and functional outcomes following ischemic stroke: A bidirectional Mendelian randomization study.
Eur J Neurol
; 31(2): e16123, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-37961927
ABSTRACT
OBJECTIVES:
Previous observational studies have indicated correlations between various inflammatory cytokines and functional outcomes following ischemic stroke (IS); however, the causality remains unclear. We aimed to further evaluate the causal association between 41 circulating inflammatory cytokines and functional outcomes following IS.METHODS:
Two-sample bidirectional Mendelian randomization (MR) analysis was used in this study. The genetic variation of 41 circulating inflammatory cytokines were derived from genome-wide association study (GWAS) data of European ancestry (n = 8293). The corresponding genetic association of functional outcomes following IS were derived from European ancestry GWAS data (n = 6021).RESULTS:
Inverse variance weighted (IVW) analysis showed that genetically predicted increased levels of regulation and activation in normal T-cell expression and secretion factor (RANTES/CCL5) and eosinophilic chemotactic factor (EOTAXIN/CCL11) were positively correlated with the increased adverse functional outcomes (modified Rankin Scale [mRS≥3] following IS (OR 1.40, 95% CI 1.002-1.96, p = 0.049; OR 1.33, 95% CI 1.15-1.54, p = 0.0001). Interleukin 18 (IL-18) level might be the downstream consequence of adverse functional outcomes following IS (ß -0.09, p = 0.039). Other inflammatory cytokines and functional outcomes following IS did not appear to be causally related.CONCLUSIONS:
This study suggests a causality between inflammation and adverse functional outcomes following IS. RANTES (CCL5) and EOTAXIN (CCL11) may be the upstream factors of adverse functional outcomes following IS, while IL-18 may be the downstream effect of adverse functional outcomes following IS. Whether these cytokines can be used to predict or improve adverse functional outcomes after IS requires further researches.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citocinas
/
AVC Isquêmico
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article