DNA methylation predicts adverse outcomes of coronary artery disease

Area of Science:

• Epigenetics
• Cardiovascular Research
• Genomics

Background:

• Coronary artery disease (CAD) is a major global cause of mortality.
• Adverse outcomes like myocardial infarction (MI) and stroke are significant complications of CAD.
• Predictive biomarkers for CAD prognosis are crucial for timely intervention.

Purpose of the Study:

• To identify DNA methylation markers associated with future mortality in CAD patients.
• To investigate the correlation of these markers with clinical and biological factors.
• To develop and validate a prognostic model for CAD using DNA methylation data.

Main Methods:

• Profiling DNA methylation in blood leukocytes from 933 Chinese CAD patients.
• Utilizing up to 13-year follow-up data from three centers.
• Correlating differentially methylated sites (DMPs) with clinical outcomes, inflammation, cardiac function, and gene expression.

Main Results:

• Identified 70 DMPs linked to future death in CAD patients.
• These DMPs correlated with inflammation, left ventricular function, and HDL cholesterol.
• Discovered FKBP5 as a key gene regulated by specific methylation sites, with its upregulation linked to MI and stroke.
• A prognostic model incorporating 10 methylation sites and 5 clinical features showed superior performance compared to traditional models.

Conclusions:

• DNA methylation patterns in blood serve as valuable predictors of prognosis in CAD.
• Epigenetic markers, such as those regulating FKBP5, play a role in CAD progression and adverse events.
• The developed prognostic model holds potential for clinical translation in improving CAD patient management.