Alterations of 5-Hydroxymethylcytosines in Circulating Cell-free DNA Reflect Retinopathy in Type 2 Diabetes

Diabetic retinopathy (DR) is a common microvascular complication that may cause severe visual impairment and blindness in patients with type 2 diabetes mellitus (T2DM). Early detection of DR will provide opportunities for more treatment options and better control of disease progression. Effective biomarkers, which are not currently available, may improve clinical outcomes through precise diagnosis and prognosis. We sought to develop a non-invasive diagnostic approach for diabetic retinopathy among type 2 diabetes mellitus based on 5-hydroxymethylcytosines (5hmC), an emerging epigenetic marker, in circulating cell-free DNA (cfDNA) We obtained genome-wide 5hmC profiles using the 5hmC-Seal technique in cfDNA samples from 70 prospectively enrolled Chinese patients, within 35 patients diagnosed with DR and 35 age-, gender-, diabetic duration-matched T2DM controls. The 5hmC-based marker genes for DR were developed using the elastic net regularization under a case-control design