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

doi:10.1016/j.diabres.2023.110918

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

Diabetes Res Clin Pract. 2023 Oct:204:110918. doi: 10.1016/j.diabres.2023.110918. Epub 2023 Sep 24.

Authors

Ishant Khurana¹, Natasha J Howard², Scott Maxwell¹, Anelle Du Preez³, Harikrishnan Kaipananickal¹, James Breen⁴, Sam Buckberry⁴, Jun Okabe¹, Keith Al-Hasani¹, Soontaree Nakasatien⁵, Thep Himathongkam⁵, Mark E Cooper⁶, Louise Maple-Brown⁷, Yotsapon Thewjitcharoen⁵, Alex Brown⁸, Assam El-Osta⁹

Affiliations

¹ Baker Heart and Diabetes Institute, Epigenetics in Human Health and Disease Program, Melbourne, Vic, Australia; Department of Diabetes, Central Clinical School, Monash University, Melbourne, Vic, Australia.
² Wardliparingga Aboriginal Health Equity Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Faculty of Health and Medical Sciences, University of Adelaide, South Australia, Australia.
³ Wardliparingga Aboriginal Health Equity Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
⁴ National Centre for Indigenous Genomics, Australian National University, Canberra, ACT, Australia; Telethon Kids Institute, Perth, WA, Australia.
⁵ Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand.
⁶ Department of Diabetes, Central Clinical School, Monash University, Melbourne, Vic, Australia.
⁷ Menzies School of Health Research, Charles Darwin University, Northern Territory, Australia; Department of Endocrinology, Royal Darwin Hospital, Northern Territory, Australia.
⁸ National Centre for Indigenous Genomics, Australian National University, Canberra, ACT, Australia; Telethon Kids Institute, Perth, WA, Australia. Electronic address: alex.brown@anu.edu.au.
⁹ Baker Heart and Diabetes Institute, Epigenetics in Human Health and Disease Program, Melbourne, Vic, Australia; Department of Diabetes, Central Clinical School, Monash University, Melbourne, Vic, Australia; University College Copenhagen, Faculty of Health, Department of Technology, Biomedical Laboratory Science, Copenhagen, Denmark. Electronic address: sam.el-osta@baker.edu.au.

PMID: 37748713
DOI: 10.1016/j.diabres.2023.110918

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.

Keywords: DNA methylation; Diabetic kidney disease; Epigenomics; Gene expression; Indigenous Aboriginal Australians; Population diversity.

MeSH terms

Albuminuria / complications
Australia
Biomarkers
Diabetes Mellitus, Type 2* / complications
Diabetic Nephropathies* / diagnosis
Diabetic Nephropathies* / genetics
Diabetic Nephropathies* / metabolism
Disease Susceptibility / complications
Epigenomics
Glomerular Filtration Rate
Humans
Kidney

Substances

Biomarkers