DNA methylation predicts adverse outcomes of coronary artery disease
Adverse outcomes including myocardial infarction (MI) and stroke render coronary artery disease (CAD) a leading cause of death worldwide. DNA methylation markers may alert such adversity ahead of the events. We profiled DNA methylation of blood leukocytes in 933 Chinese CAD patients with up-to-13-year follow-up from three centers, identifying 70 differentially methylated sites (DMPs) associated with future death. These DMPs correlated with inflammation markers, left ventricular functions and high-density lipoprotein cholesterol, and impacted gene expression in immune response and cellular scenesence. Notably, cg25563198 and cg25114611 were discovered to regulate FKBP5, whose upregulation persisted during MI and stroke. Fkbp5 knockout in male mice partially rescued MI by reducing infarct size and improving heart function, confirming its critical function. Finally, our prognostic model of 10 methylation sites and 5 clinical features outperformed clinical models. Our study highlights the value of DNA methylation in predicting prognosis in CAD and provides tools for clinical translation.
Authors
- Min Qin (ORCID: https://orcid.org/0009-0000-5632-7756)
- Cuiping Pan (ORCID: https://orcid.org/0000-0002-8152-2489)
- Qili Wu
- Qian Zhu (ORCID: https://orcid.org/0009-0002-4340-5844)
- Xipei Wang (ORCID: https://orcid.org/0000-0002-2017-7247)
- Xianhong Fang (ORCID: https://orcid.org/0000-0002-5290-0954)
- Shilong Zhong (ORCID: https://orcid.org/0000-0002-2696-7696)
- Xiaoxue Tian (ORCID: https://orcid.org/0009-0003-0950-3747)
- Chen Liu (ORCID: https://orcid.org/0000-0002-9818-0454)
- Bin Zhang (ORCID: https://orcid.org/0000-0002-6631-7647)
- Xiaoping Chen (ORCID: https://orcid.org/0000-0002-2910-9152)
- Meiling Yu
- Hanping Li
Institutions
- Central South University (CN)
- Sun Yat-sen University (CN)
- Shanghai Jiao Tong University (CN)
- Hong Kong University of Science and Technology (HK)
- Kunming Medical University (CN)
- Shanghai Children's Medical Center (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Guangdong Academy of Medical Sciences (CN)
- First Affiliated Hospital of Bengbu Medical College (CN)
- Guangdong Provincial People's Hospital (CN)
- Guangzhou HKUST Fok Ying Tung Research Institute (CN)
- Xiangya Hospital Central South University (CN)
- Southern Medical University (CN)
- University of Hong Kong (HK)
- South China University of Technology (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1038/s41467-025-66204-x
- Citations
- 1
- Primary Topic
- Signaling Pathways in Disease
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Natural Science Foundation of China
- Guangdong Provincial People's Hospital
- National Key Research and Development Program of China