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
N1 - Funding Information:
We thank Prof. Paul Zimmet for the continued support and guidance with the PROPHECY Aboriginal Diabetes Study. We acknowledge Alai Lezama for the PROPHECY laboratory assistance for the Aboriginal Diabetes Study sample collection and curation. The authors gratefully acknowledge the support of PROPHECY (Aboriginal Diabetes Study) participants, study staff, partner organisations and participating health and community services in South Australia. The authors wish to thank all attending staffs at Diabetes and Thyroid Center, Theptarin Hospital for their continued support and cooperation in recruiting participating people without and those people that live with diabetes. AE-O is a National Health and Medical Research Council (NHMRC) Senior Research Fellow (APP1154650) and acknowledges grant support NHMRC Clinical Trials and Cohort Studies Grant (APP2014763). PROPHECY Cohort Study was supported by funding from NHMRC Project Grant (APP1086386), NHMRC Clinical Trials and Cohort Grant (APP2006883), MRFF Indigenous Health Round (MRFF APP1200005) and The Hospital Research Foundation (S-01-RSRCH). AB was supported by a NHMRC Senior Research Fellowship (APP1137563). LMB was supported by Australian NHMRC Investigator Grant (APP1194698). IK, SM, HK, JB, SB, JO, performed the investigation, validation and data visualization, IK, NJH, SM, HK, JB, SB, JO, KA-H were involved in data curation, software and methodology, NJH, ADP, SN, TH, YT, AB were involved in provision of resources and methodology of population cohorts.TH, MEC, LM-B, YT, AB, AE-O were involved in conceptualization, supervision, project administration and funding acquisition. AE-O wrote the first draft of the manuscript, and all authors edited, reviewed, and approved the final version of the manuscript. AE-O is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation, None.
Funding Information:
AE-O is a National Health and Medical Research Council (NHMRC) Senior Research Fellow (APP1154650) and acknowledges grant support NHMRC Clinical Trials and Cohort Studies Grant (APP2014763). PROPHECY Cohort Study was supported by funding from NHMRC Project Grant (APP1086386), NHMRC Clinical Trials and Cohort Grant (APP2006883), MRFF Indigenous Health Round (MRFF APP1200005) and The Hospital Research Foundation (S-01-RSRCH). AB was supported by a NHMRC Senior Research Fellowship (APP1137563). LMB was supported by Australian NHMRC Investigator Grant (APP1194698).
Publisher Copyright:
© 2023 The Author(s)
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 - Diabetic kidney disease
KW - DNA methylation
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
C2 - 37748713
AN - SCOPUS:85172670184
SN - 0168-8227
VL - 204
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
M1 - 110918
ER -