Cytosine Methylation Studies in Patients with Diabetic Kidney Disease
Purpose of the Review
Kidney disease is the major cause of morbidity and mortality in patients with diabetes. Poor glycemic control shows the strongest correlation with diabetic kidney disease (DKD) development. A period of poor glycemia increases kidney disease risk even after an extended period of improved glucose control—a phenomenon called metabolic memory. Changes in the epigenome have been proposed to mediate the metabolic memory effect, as epigenome editing enzymes are regulated by substrates of intermediate metabolism and changes in the epigenome can be maintained after cell division.
Epigenome-wide association studies (EWAS) have reported differentially methylated cytosines in blood and kidney samples of DKD subjects when compared with controls. Differentially methylated cytosines were enriched on regulatory regions and some correlated with gene expression. Methylation changes predicted the speed of kidney function decline. Site-specific methylome editing tools now can be used to interrogate the functional role of differentially methylated regions.
Methylome changes can be detected in blood and kidneys of patients with DKD. Methylation changes can predict future kidney function changes. Future studies shall determine their role in disease development.
KeywordsEpigenetics Cytosine methylation Diabetic kidney disease Epigenome editing Epigenome-wide association analysis (EWAS) Metabolic memory
Compliance with Ethical Standards
Conflict of Interest
Tamas Aranyi declares that he has no conflict of interest.
Katalin Susztak reports grant support from GSK, Regeneron, Boehringer Ingelheim, Merck, Bayer, Eli Lilly and Company, and Gilead; and consulting for Chemocentryx, Janssen, and Maze Bio. However, the work is not related to any of the studies supported by industry.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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