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Differentially hypomethylated cell-free DNA and coronary collateral circulation

 Jongseong Ahn  ;  Sunghoon Heo  ;  Soo-Jin Ahn  ;  Duhee Bang  ;  Sang-Hak Lee 
 CLINICAL EPIGENETICS, Vol.14(1) : 140, 2022-11 
Journal Title
Issue Date
Case-Control Studies ; Cell-Free Nucleic Acids* ; Collateral Circulation ; Coronary Artery Disease* ; DNA Methylation ; Female ; Humans ; Male ; Middle Aged
Biomarkers ; Cell-free DNA ; Coronary artery disease ; DNA methylation ; Differentially methylated regions ; Random forest
Background: The factors affecting cardioprotective collateral circulation are still incompletely understood. Recently, characteristics, such as CpG methylation of cell-free DNA (cfDNA), have been reported as markers with clinical utility. The aim of this study was to evaluate whether cfDNA methylation patterns are associated with the grade of coronary collateral circulation (CCC).

Result: In this case-control study, clinical and angiographic data were obtained from 143 patients (mean age, 58 years, male 71%) with chronic total coronary occlusion. Enzymatic methyl-sequencing (EM-seq) libraries were prepared using the cfDNA extracted from the plasma. Data were processed to obtain the average methylation fraction (AMF) tables of genomic regions from which blacklisted regions were removed. Unsupervised analysis of the obtained AMF values showed that some of the changes in methylation were due to CCC. Through random forest preparation process, 256 differentially methylated region (DMR) candidates showing strong association with CCC were selected. A random forest classifier was then constructed, and the area under the curve of the receiver operating characteristic curve indicated an appropriate predictive function for CCC. Finally, 20 DMRs were identified to have significantly different AMF values between the good and poor CCC groups. Particularly, the good CCC group exhibited hypomethylated DMRs. Pathway analysis revealed five pathways, including TGF-beta signaling, to be associated with good CCC.

Conclusion: These data have demonstrated that differential hypomethylation was identified in dozens of cfDNA regions in patients with good CCC. Our results support the clinical utility of noninvasively obtained epigenetic signatures for predicting collateral circulation in patients with vascular diseases.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Ann, Soo Jin(안수진)
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
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