How epigenetics impacts stroke risk and outcomes through DNA methylation: A systematic review

Gallego-Fabrega C, Cullell N, Fernández-Cadenas I. J Cereb Blood Flow Metab. 2025 Feb 27:271678X251322032. doi: 10.1177/0271678X251322032. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/40012472/

Abstract: The impact of DNA methylation (DNAm) on epigenetics has gained prominence in recent years due to its potential influence on ischemic stroke (IS) and treatment outcomes. DNAm is reversible and a better understanding of its role in IS could help identify novel therapeutic targets. The aim of this systematic review was to compile the available data on DNAminthe risk and prognosis of IS and to explore its therapeutic potential. The review process followed the PRISMA criteria. We searched the Pubmed and Cochrane databases to identify studies that used hypothesis free methodological approaches. Of the 459 studies identified, 34 met the inclusion criteria. The studies were categorized as follows: risk of IS; outcomes; and DNAm age. Most studies used genotyping array technology rather than whole-genome sequencing. DNAm testing was mainly based on blood samples. Most studies involved European cohorts. Most of the studies were performed at a single-center with recruitment at the time of stroke. In a few studies, health status was determined longitudinally. This systematic review shows that IS patients are biologically older than expected and present characteristic DNAm patterns related to stroke risk and outcomes. These patterns could be used to develop new treatments with epidrugs.

Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study is partially supported by the projects: COPYCTUS (PI21/01088), EPINEXO (PI20/00678), PREVICTUS (PMP21/ 00165) and RICORS-ICTUS (RD21/0006/0006, RD24/0009/ 0029 and RD24/0009/0010) from Instituto de Salud Carlos III (ISCIII, Fondos FEDER/FSE) and STOPPED-Stroke (20231030-31-32) from La Marato Foundation.