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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

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 language	English
Article number	110918
Journal	Diabetes Research and Clinical Practice
Volume	204
DOIs	https://doi.org/10.1016/j.diabres.2023.110918
Publication status	Published - Oct 2023

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10.1016/j.diabres.2023.110918

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Khurana, I., Howard, N. J., Maxwell, S., Du Preez, A., Kaipananickal, H., Breen, J., Buckberry, S., Okabe, J., Al-Hasani, K., Nakasatien, S., Himathongkam, T., Cooper, M. E., Maple-Brown, L., Thewjitcharoen, Y., Brown, A., & El-Osta, A. (2023). Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus. Diabetes Research and Clinical Practice, 204, Article 110918. https://doi.org/10.1016/j.diabres.2023.110918

@article{0bc7bda24f044966b64c07a01943c0fd,

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

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",

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

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = oct,

doi = "10.1016/j.diabres.2023.110918",

language = "English",

volume = "204",

journal = "Diabetes Research and Clinical Practice",

issn = "0168-8227",

publisher = "Elsevier Ireland Ltd",

}

Khurana, I, Howard, NJ, Maxwell, S, Du Preez, A, Kaipananickal, H, Breen, J, Buckberry, S, Okabe, J, Al-Hasani, K, Nakasatien, S, Himathongkam, T, Cooper, ME, Maple-Brown, L, Thewjitcharoen, Y, Brown, A & El-Osta, A 2023, 'Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus', Diabetes Research and Clinical Practice, vol. 204, 110918. https://doi.org/10.1016/j.diabres.2023.110918

TY - JOUR

T1 - Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus

AU - Khurana, Ishant

AU - Howard, Natasha J.

AU - Maxwell, Scott

AU - Du Preez, Anelle

AU - Kaipananickal, Harikrishnan

AU - Breen, James

AU - Buckberry, Sam

AU - Okabe, Jun

AU - Al-Hasani, Keith

AU - Nakasatien, Soontaree

AU - Himathongkam, Thep

AU - Cooper, Mark E.

AU - Maple-Brown, Louise

AU - Thewjitcharoen, Yotsapon

AU - Brown, Alex

AU - El-Osta, Assam

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

KW - DNA methylation

KW - Diabetic kidney disease

KW - Epigenomics

KW - Gene expression

KW - Indigenous Aboriginal Australians

KW - Population diversity

UR - http://www.scopus.com/inward/record.url?scp=85172670184&partnerID=8YFLogxK

U2 - 10.1016/j.diabres.2023.110918

DO - 10.1016/j.diabres.2023.110918

M3 - Article

SN - 0168-8227

VL - 204

JO - Diabetes Research and Clinical Practice

JF - Diabetes Research and Clinical Practice

M1 - 110918

ER -

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

Abstract

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