RT Journal Article
T1 Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study.
A1 Cullell, Natalia
A1 Soriano-Taraga, Carolina
A1 Gallego-Fabrega, Cristina
A1 Carcel-Marquez, Jara
A1 Muiño, Elena
A1 Llucia-Carol, Laia
A1 Lledos, Miquel
A1 Esteller, Manel
A1 de-Moura, Manuel Castro
A1 Montaner, Joan
A1 Rosell, Anna
A1 Delgado, Pilar
A1 Marti-Fabregas, Joan
A1 Krupinski, Jerzy
A1 Roquer, Jaume
A1 Jimenez-Conde, Jordi
A1 Fernandez-Cadenas, Israel
K1 Brain Ischemia
K1 DNA Methylation
K1 Epigenome
K1 Humans
K1 Stroke
AB The neurological course after stroke is highly variable and is determined by demographic, clinical and genetic factors. However, other heritable factors such as epigenetic DNA methylation could play a role in neurological changes after stroke. We performed a three-stage epigenome-wide association study to evaluate DNA methylation associated with the difference between the National Institutes of Health Stroke Scale (NIHSS) at baseline and at discharge (ΔNIHSS) in ischaemic stroke patients. DNA methylation data in the Discovery (n = 643) and Replication (n = 62) Cohorts were interrogated with the 450 K and EPIC BeadChip. Nominal CpG sites from the Discovery (p value  The meta-analysis revealed an epigenome-wide significant association in EXOC4 (p value = 8.4 × 10-08) and in MERTK (p value = 1.56 × 10-07). Only the methylation in EXOC4 was also associated in the Discovery and in the Replication Cohorts (p value = 1.14 × 10-06 and p value = 1.3 × 10-02, respectively). EXOC4 methylation negatively correlated with the long-term outcome (coefficient = - 4.91) and showed a tendency towards a decrease in EXOC4 expression (rho = - 0.469, p value = 0.091). Pathway enrichment from the meta-analysis revealed significant associations related to the endocytosis and deubiquitination processes. Seventy-nine plasma proteins were differentially expressed in association with EXOC4 methylation. Pathway analysis of these proteins showed an enrichment in natural killer (NK) cell activation. The cell-type methylation analysis in blood also revealed a differential methylation in NK cells. DNA methylation of EXOC4 is associated with a worse neurological course after stroke. The results indicate a potential modulation of pathways involving endocytosis and NK cells regulation.
PB BioMed Central Ltd.
YR 2022
FD 2022-09-30
LK http://hdl.handle.net/10668/20359
UL http://hdl.handle.net/10668/20359
LA en
NO Cullell N, Soriano-Tárraga C, Gallego-Fábrega C, Cárcel-Márquez J, Muiño E, Llucià-Carol L, et al. Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study. Clin Epigenetics. 2022 Sep 30;14(1):124.
DS RISalud
RD Apr 6, 2025