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Abstract Details

Genome-wide DNA methylation profiling in peripheral blood from different TOAST-subtypes stroke patients.
Cerebrovascular Disease and Interventional Neurology
P4 - Poster Session 4 (5:30 PM-6:30 PM)
3-046
Our aim was to assess genome-wide DNA methylation signatures of stroke patients with different TOAST etiologies in order to discover novel epigenetic biomarkers related to stroke etiology.  
Stroke is the fifth leading cause of death and the leading cause of adult disability in the U.S. Identify his etiology lets clinician improve an adequate secondary prevention approach. 
We profiled genome-wide DNA methylation levels in blood samples from a cohort of well-characterized atherothrombotic (n=8), cardioembolic (n=14) and undetermined (n=8) (TOAST) patients (n=30) by  using the Infinium MethylationEPIC (Illumina) array which quantitatively assays over 850,000 CpG sites across the genome at single-nucleotide resolution. BMIQ procedure was used to normalize the results. 

We identified sets of differentially methylated positions (DMPs) in pair-wise comparisons (cut-off criteria delta >0.2 & p-value <0.05): atherothrombotic vs undetermined (182 DMPs), cardioembolic vs undetermined (159 DMPs) and atherothrombotic vs cardioembolic (132 DMPs), the latter being the most interesting comparison to discover new etiologic biomarkers with clinical implications. Most of these 132 DMPs were hypermethylated in atherothrombotic compared to cardioembolic patients (65.6%). DMPs preferentially overlapped gene body (36.6%) and intergenic regions (38.9%). Among the top-ranked DMPs, we found sites localized in genes identified in a literature review as possibly related with stroke and his pathogenesis: AGPAT9, LMF1 and TP53INP2.

 

Genome-wide DNA methylation profiling may help to identify novel candidate epigenetic biomarkers to help in the etiology diagnosis of stroke. Further studies in other cohorts will be needed to study the role of these epigenetic variants as etiology biomarkers.  
Authors/Disclosures
Juan Marta-Enguita, MD (Osasunbidea)
PRESENTER
No disclosure on file
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Jaime G. Gallego, MD No disclosure on file
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