Bioanalytical
Epigenetic changes boost understanding of chronic kidney disease
Nov 22 2013
Experts in the US may be a little closer to explaining chronic kidney disease, following the publication of a new study which explains that epigenetic changes could be the key to understanding the condition and how it progresses.
The new report aimed to understand the molecular roots and genetic predisposition of chronic kidney disease and involved carrying out a genome-wide survey, which revealed there are significant differences in the pattern of chemical modifications on DNA, which affect gene expression in kidney cells from patients with chronic kidney disease versus healthy controls.
The study was led by physician-scientist Dr Katalin Susztak, associate professor of medicine in the Renal Electrolyte and Hypertension Division, at the Perelman School of Medicine, University of Pennsylvania, in conjunction with John Greally from the Albert Einstein College of Medicine, Bronx, New York.
It is the first study to show that changes in these modifications – which are the cornerstone of the field of epigenetics – could explain chronic kidney disease.
In patients with chronic kidney disease, the kidneys are damaged and cannot adequately filter blood, which causes waste to build up and lead to other health problems, such as cardiovascular disease, anaemia and bone disease.
The new study looked at human kidney cells that looked almost the same under a microscope, but the way each cell type is affected by the methyl groups was very different; generally, they observed that an increase in the number of methyl groups on a gene turns off expression, while a decrease of methyl groups turns on a gene's expression.
In particular, the experts found that the differences in the methyl groups were not on promoter regions in the diseased kidney cells, but mostly on enhancer regions, and were also near sequences for important kidney transcription factors - something that speaks to the importance of these regions in regulating gene expression, Dr Susztak explained.
"Most of the research on kidney epigenetics so far has been on promoter regions on kidney cancer cells," she said.
"The difference we found in dysregulation between the two cell populations may indicate that dysregulation in cancer is different from dysregulation in chronic kidney disease. Five years ago there was no epigenetic information outside of cancer."
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