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Original Article

IJMDC. 2025; 9(10): 2430-2442


Epigenetic signature in atherosclerosis: a novel discovery of ODF2 methylation linked to unstable plaque and stroke risk stratification in the Emergency Department

Feras Ahmed Aljarri, Waleed Khalid Moosa, Hadi Abdulkarim Al Nas, Mahdi Abdulwahed Alsaeed, Sarah Albasha, Dunya Alfaraj, Abdullah Maher Felemban, Fatimah Alawami, Abdullah Alali, Abdulmonem Alsaleh.



Abstract
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Objective:
This study aimed to assess the genome-wide DNA methylation profile associated with atherosclerotic disease and to identify differentially methylated sites associated with clinical features of plaque instability.
Methods:
Using silico analysis, four publicly available 850K and 450K methylation array datasets were analyzed to identify consistently differentially methylated positions in atherosclerosis. Based on the highest methylation difference (top 20%) and significance (p-value ≤0.001), differentially methylated positions were specified.
Results:
By analyzing four publicly available methylation datasets, 506 differentially methylated genes linked to atherosclerosis were detected. Moreover, a comparative analysis between all the datasets determined four shared differentially methylated genes in only two datasets: ODF2, MTRF1L, HMCN1, and GMDS. However, further analysis revealed that only one gene, which is ODF2, exhibited a significant increase in methylation levels within the promoter area, while the others were insignificant.
Conclusion:
While further validation is required, this study provided a comprehensive methylation profile in atherosclerotic patients and highlighted the novel identification of ODF2 hypomethylation as a potential biomarker for plaque instability.

Key words: Atherosclerosis, genes, DNA methylation, promoter area, stroke







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