Genome-Wide DNA Methylation Profiling Reveals Enrichment of Developmental Vascular and Muscle Programs in Peripheral Artery Disease: A Pilot Epigenome-Wide Association Study

The study examined DNA methylation patterns in 10 patients with peripheral artery disease (PAD) and 22 healthy controls using the Infinium Methylation EPIC v2.0 platform, which analyzes over 935,000 CpG sites. After quality control, 933,942 probes were analyzed. The majority of significant methylation differences showed hypomethylation in PAD patients. Analysis of 16,854 high-confidence genes revealed enrichment in muscle system processes, embryonic organ development, and calcium and cadherin signaling. The results suggest that blood methylation patterns in PAD patients are enriched in developmental vascular and muscle programs that are reactivated in vascular pathology. The authors propose the need for larger validation studies to develop biomarkers and epigenetic therapies for PAD.