Abstract
Introduction
Prolonged hyperglycaemia in type 1 diabetes mellitus may lead to diabetic nephropathy (DN). While there is evidence that DNA methylation plays a role in the human disease, the exact nature of the covalent modification at the CG dinucleotide in the development of DN remains poorly understood. A previous study has identified a core set of genes (MTOR, RPTOR, IRS2, COL1A2, TXNRD1, LCAT and SMPD3) through methylation sequencing and showed loss of DNA methylation in correlation with progression of DN. We examined the core-genes in the “PROFIL” registry at the Steno Diabetes Center Copenhagen to assess whether DNA methylation could be used as a biomarker for predicting the progression of DN.
Material and methods
Using methylation-capture qPCR analysis, we examined DNA methylation distribution at CpG sites on the seven core-genes in blood-derived DNA from 363 individuals with type 1 diabetes mellitus from the Danish “PROFIL” registry, whereas all individuals have had diabetes of a duration of 20 years. The DNA methylation results were reported as “combined DNA methylation” and were compared to KDIGO staging and classification, albuminuria status, and decline in kidney damage and function.
Results
The methylation-capture analysis results reveal the inverse correlation between DNA methylation and progression of DN. We show significant decreasing changes in DNAm compared to the KDIGO classifications (p<0.0001) and to the albuminuria status (p<0.0001). We also report a trend of DNAm loss in the association with kidney damage progression and kidney function decline.
Conclusions
We have provided evidence of a direct mechanism of DNA methylation loss which correlates with the progression of DN. The close link between DNA methylation and the DN progression means that DNAm can be used as a qualitative biomarker for predicting the progression of DN.
Prolonged hyperglycaemia in type 1 diabetes mellitus may lead to diabetic nephropathy (DN). While there is evidence that DNA methylation plays a role in the human disease, the exact nature of the covalent modification at the CG dinucleotide in the development of DN remains poorly understood. A previous study has identified a core set of genes (MTOR, RPTOR, IRS2, COL1A2, TXNRD1, LCAT and SMPD3) through methylation sequencing and showed loss of DNA methylation in correlation with progression of DN. We examined the core-genes in the “PROFIL” registry at the Steno Diabetes Center Copenhagen to assess whether DNA methylation could be used as a biomarker for predicting the progression of DN.
Material and methods
Using methylation-capture qPCR analysis, we examined DNA methylation distribution at CpG sites on the seven core-genes in blood-derived DNA from 363 individuals with type 1 diabetes mellitus from the Danish “PROFIL” registry, whereas all individuals have had diabetes of a duration of 20 years. The DNA methylation results were reported as “combined DNA methylation” and were compared to KDIGO staging and classification, albuminuria status, and decline in kidney damage and function.
Results
The methylation-capture analysis results reveal the inverse correlation between DNA methylation and progression of DN. We show significant decreasing changes in DNAm compared to the KDIGO classifications (p<0.0001) and to the albuminuria status (p<0.0001). We also report a trend of DNAm loss in the association with kidney damage progression and kidney function decline.
Conclusions
We have provided evidence of a direct mechanism of DNA methylation loss which correlates with the progression of DN. The close link between DNA methylation and the DN progression means that DNAm can be used as a qualitative biomarker for predicting the progression of DN.
| Original language | English |
|---|---|
| Publication date | 25 Aug 2021 |
| Publication status | Published - 25 Aug 2021 |
| Event | World Congress of Biomedical Laboratory Science - Bella Center, København, Denmark Duration: 24 Aug 2021 → 28 Aug 2021 Conference number: 34 https://ifbls2020.org/ |
Conference
| Conference | World Congress of Biomedical Laboratory Science |
|---|---|
| Number | 34 |
| Location | Bella Center |
| Country/Territory | Denmark |
| City | København |
| Period | 24/08/21 → 28/08/21 |
| Internet address |