Genes involved in diabetic kidney disease identified

Monday, 16 March 2020

Kidney disease is a serious complication that develops in some people living with diabetes – both Type 1 and Type 2. That’s because diabetes affects the kidneys’ ability to filter extra water and waste products from the body and leads to high blood pressure, swollen extremities, loss of concentration, fatigue and could end in kidney failure.

“Studies have shown that diabetic kidney disease tends to run in families in some populations, suggesting a genetic predisposition,” explained Karl Tryggvason, Professor in Diabetes Research at Duke-NUS’ Medical School.

However, identifying the specific genes involved has remained a challenge. Scientists also still don’t know precisely how diabetic kidney disease develops at the molecular level.

About the research

Prof Tryggvason led a team that focused on analyzing genes in Finns. “This population is uniquely homogeneous and has the world’s highest incidence of Type 1 diabetes.  They have accumulated rare genetic traits that can help in genetic studies of diseases.”

The team compared the genomes of 76 Finnish sibling pairs, where both siblings had Type 1 diabetes for more than 15 years but only one had developed diabetic kidney disease. They looked for differences between the siblings at the genome, gene, and single mutation level.

They then validated their results by analyzing the genes of more than 3,500 unrelated Finns with Type 1 diabetes, almost 40 per cent of whom had diabetic kidney disease.

Their analysis found several genes that could be involved in the development of the disease by coding for mutations in protein-modifying enzymes belonging to a large family of proteins called protein kinase C.  These proteins are essential for the function of cells involved in filtering blood inside the kidneys, and could be attractive targets for treating diabetic kidney disease.

What do the results mean?

Prof Tryggvason’s diabetes research among Finns has advanced the understanding of diabetic kidney disease worldwide. The findings have major implications for the development of better prevention and treatment strategies.”

Further investigations are needed in other populations and in pre-clinical models of the disease to confirm the roles of these genes and proteins in the condition. Duke-NUS researchers are now sequencing the genomes of 1,000 Singaporeans with diabetes to compare with the findings from the Finnish study. This collaboration with researchers from Singapore aims to further improve the understanding of diabetic kidney disease and working to reduce its prevalence.

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