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Differentially hypomethylated cell-free DNA and coronary collateral circulation
Jongseong Ahn1, Sunghoon Heo2, Soo-Jin Ahn3
1Department of Chemistry, Yonsei University, 50, Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Clinical Epigenetics
|November 2, 2022
Summary
Cell-free DNA (cfDNA) methylation patterns can predict coronary collateral circulation (CCC) in patients with vascular disease. Good CCC is associated with differential hypomethylation in specific cfDNA regions, supporting epigenetic signatures for clinical use.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Genomics
Background:
- Cardioprotective collateral circulation is crucial but not fully understood.
- Cell-free DNA (cfDNA) methylation is emerging as a potential clinical marker.
- The association between cfDNA methylation patterns and coronary collateral circulation (CCC) grade requires investigation.
Purpose of the Study:
- To investigate the relationship between cfDNA methylation patterns and the grade of coronary collateral circulation (CCC).
- To assess the potential of cfDNA methylation as a non-invasive biomarker for predicting collateral circulation.
Main Methods:
- A case-control study involving 143 patients with chronic total coronary occlusion.
- Plasma cfDNA was analyzed using enzymatic methyl-sequencing (EM-seq).
- Differential methylation analysis and random forest classification were employed to identify regions associated with CCC grade.
Main Results:
- Unsupervised analysis revealed methylation changes correlated with CCC.
- 256 differentially methylated region (DMR) candidates were identified, with 20 showing significant differences between good and poor CCC groups.
- The good CCC group exhibited hypomethylated DMRs, and pathway analysis implicated TGF-beta signaling.
Conclusions:
- Differential hypomethylation in cfDNA regions is linked to good CCC.
- Epigenetic signatures from cfDNA show clinical utility for predicting collateral circulation.
- This supports the use of non-invasive epigenetic markers in vascular disease management.

