Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus

Ishant Khurana, Natasha J. Howard, Scott Maxwell, Anelle Du Preez, Harikrishnan Kaipananickal, James Breen, Sam Buckberry, Jun Okabe, Keith Al-Hasani, Soontaree Nakasatien, Thep Himathongkam, Mark E. Cooper, Louise Maple-Brown, Yotsapon Thewjitcharoen, Alex Brown, Assam El-Osta

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Aims: To investigate epigenomic indices of diabetic kidney disease (DKD) susceptibility among high-risk populations with type 2 diabetes mellitus. Methods: KDIGO (Kidney Disease: Improving Global Outcomes) clinical guidelines were used to classify people living with or without DKD. Differential gene methylation of DKD was then assessed in a discovery Aboriginal Diabetes Study cohort (PROPHECY, 89 people) and an external independent study from Thailand (THEPTARIN, 128 people). Corresponding mRNA levels were also measured and linked to levels of albuminuria and eGFR. Results: Increased DKD risk was associated with reduced methylation and elevated gene expression in the PROPHECY discovery cohort of Aboriginal Australians and these findings were externally validated in the THEPTARIN diabetes registry of Thai people living with type 2 diabetes mellitus. Conclusions: Novel epigenomic scores can improve diagnostic performance over clinical modelling using albuminuria and GFR alone and can distinguish DKD susceptibility.

Original languageEnglish
Article number110918
JournalDiabetes Research and Clinical Practice
Volume204
ISSN0168-8227
DOIs
Publication statusPublished - Oct 2023

Keywords

  • Diabetic kidney disease
  • DNA methylation
  • Epigenomics
  • Gene expression
  • Indigenous Aboriginal Australians
  • Population diversity

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