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Translational Stroke Research

23-04-2024 | Epigenetics | Research

Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage

Authors: Isabel Fernández-Pérez, Joan Jiménez-Balado, Adrià Macias-Gómez, Antoni Suárez‑Pérez, Marta Vallverdú-Prats, Alberto Pérez-Giraldo, Marc Viles-García, Julia Peris-Subiza, Sergio Vidal-Notari, Eva Giralt-Steinhauer, Daniel Guisado-Alonso, Manel Esteller, Ana Rodriguez-Campello, Jordi Jiménez-Conde, Angel Ois, Elisa Cuadrado-Godia

Published in: Translational Stroke Research

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Abstract

Vasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850 K CpG sites) in whole-blood samples collected at hospital admission. We identified differentially methylated positions (DMPs) at the CpG level using Cox regression models adjusted for potential confounders, and then we used the DMP results to find differentially methylated regions (DMRs) and enriched biological pathways. A total of 145 patients (51%) experienced vasospasm. In the DMP analysis, we identified 31 CpGs associated with vasospasm at p-value < 10−5. One of them (cg26189827) was significant at the genome-wide level (p-value < 10−8), being hypermethylated in patients with vasospasm and annotated to SUGCT gene, mainly expressed in arteries. Region analysis revealed 13 DMRs, some of them annotated to interesting genes such as POU5F1, HLA-DPA1, RUFY1, and CYP1A1. Functional enrichment analysis showed the involvement of biological processes related to immunity, inflammatory response, oxidative stress, endothelial nitric oxide, and apoptosis. Our findings show, for the first time, a distinctive epigenetic signature of vasospasm in aSAH, establishing novel links with essential biological pathways, including inflammation, immune responses, and oxidative stress. Although further validation is required, our results provide a foundation for future research into the complex pathophysiology of vasospasm.
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Metadata
Title
Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage
Authors
Isabel Fernández-Pérez
Joan Jiménez-Balado
Adrià Macias-Gómez
Antoni Suárez‑Pérez
Marta Vallverdú-Prats
Alberto Pérez-Giraldo
Marc Viles-García
Julia Peris-Subiza
Sergio Vidal-Notari
Eva Giralt-Steinhauer
Daniel Guisado-Alonso
Manel Esteller
Ana Rodriguez-Campello
Jordi Jiménez-Conde
Angel Ois
Elisa Cuadrado-Godia
Publication date
23-04-2024
Publisher
Springer US
Published in
Translational Stroke Research
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-024-01252-x