Genome-wide analysis reflects novel 5-hydroxymethylcytosines implicated in diabetic nephropathy and the biomarker potential

Ying Yang, Chang Zeng, Kun Yang, Shaohua Xu, Zhou Zhang, Qinyun Cai, Chuan He, Wei Zhang*, Song Mei Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Aim: Diabetic nephropathy (DN) has become the most common cause of end-stage renal disease in most countries for patients with type 2 diabetes (T2D). Elucidating novel epigenetic contributors to DN can not only enhance our understanding of this complex disorder but also lay the foundation for developing more effective monitoring tools and preventive interventions in the future, thus contributing to our ultimate goal of improving patient care. Methods: 5-hydroxymethylcytosines (5hmC)-Seal, a highly selective chemical labeling technique, was used to profile genome-wide 5hmC, a stable cytosine modification type marking gene activation, in circulating cell-free DNA (cfDNA) samples from a cohort of patients recruited at Zhongnan Hospital, including T2D patients with nephropathy (DN, n = 12), T2D patients with non-DN vascular complications (non-DN, n = 29), and T2D patients without any complication (controls, n = 14). Differential analysis was performed to find DN-associated 5hmC features, followed by the exploration of biomarker potential of 5hmC in cfDNA for DN using a machine learning approach. Results: Genome-wide analyses of 5hmC in cfDNA detected 427 and 336 differential 5hmC modifications associated with DN, compared with non-DN individuals and controls, and suggested relevant pathways such as NOD-like receptor signaling pathway and tyrosine metabolism. Our exploration using a machine learning approach revealed an exploratory model comprised of ten 5hmC genes showing the possibility to distinguish DN from non-DN individuals or controls. Conclusion: Genome-wide analysis suggests the possibility of exploiting novel 5hmC in patient-derived cfDNA as a non-invasive tool for monitoring DN in high-risk T2D patients in the future.

Original languageEnglish (US)
Pages (from-to)49-60
Number of pages12
JournalExtracellular Vesicles and Circulating Nucleic Acids
Issue number1
StatePublished - 2022


  • 5-hydroxymethylcytosine
  • Type 2 diabetes
  • cfDNA
  • epigenetics
  • nephropathy

ASJC Scopus subject areas

  • Cell Biology


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