Genome-wide Analysis Reflects Novel 5-Hydroxymethylcytosines Implicated in Diabetic Nephropathy

Background: Long-term complications of type 2 diabetes (T2D) are the major causes for T2D-related disability and mortality. Notably, diabetic nephropathy (DN) has become the most frequent cause of end-stage renal disease (ESRD) in most countries. Understanding epigenetic contributors to DN can provide novel insights into this complex disorder and lay the foundation for more effective monitoring tools and preventive interventions, critical for achieving the ultimate goal of improving patient care and reducing healthcare burden. The 5hmC-Seal, a selective chemical labeling technique was used to profile genome-wide 5-hydroxymethylcytosines (5hmC), an emerging class of cytosine modifications, in patient-derived circulating cell-free DNA (cfDNA). Differentially modified 5hmC genes were identified across T2D patients with DN (n = 12), T2D patients with non-DN vascular complications (non-DN) (n = 29), and T2D patients with no complications (controls) (n = 14).