GSE134766
DNA methylation patterns from peripheral blood separate coronary artery disease patients with and without heart failure.
Coronary artery disease (CAD) and ischaemic cardiomyopathy are leading causes of mortality and morbidity worldwide. Currently there are only two well established biomarkers used for heart failure diagnosis and prognosis. Therefore, more research into the genetic and epigenetic mechanisms of heart failure (HF) will allow identification of biomarkers that can be used for different stages of HF. DNA methylation is an epigenetic mark that is increasingly recognised to play a critical role in cardiovascular disease. However, there are no methylation studies that specifically focus on ischaemic cardiomyopathy. Here we performed a small scale methylome wide association study to identify epigenetic markers in peripheral blood in a cohort of patients with and without HF who otherwise share a similar coronary ischaemic burden, age, sex, and ethnicity. We identified 68 significantly differentially methylated regions in our data. Of these regions, 48 occurred within gene bodies and 25 were located near enhancer elements, some within coding genes and some in non-coding genes. Our gene set enrichment analyses identified 103 significantly enriched gene sets in HF. We have demonstrated the utility of methyl-binding domain capture sequencing to evaluate DNA methylation markers in a perioperative cohort of cardiac surgical patients with ischaemic cardiomyopathy and HF. The peripheral methylation status of specific coding genes, such as HDAC9, are candidates for larger longitudinal studies. We have further demonstrated the value and feasibility of examining DNA methylation patterns from peripheral blood to highlight cellular pathways and processes that may contribute to the development of HF. Overall design: Here we applied MBD-seq to perform a small scale methylome wide association study to identify epigenetic markers in peripheral blood in a cohort of patients with (n=10) and without HF (n=10) who otherwise share a similar coronary ischaemic burden, age, sex, and ethnicity.