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January 2, 2008

SickKids scientists discover one of the genetic variations responsible for kidney failure in diabetics

Toronto - Following a two-year genetic association study, scientists at The Hospital for Sick Children (SickKids) have discovered that variations in the gene SOD1 are linked to the development and progression of diabetic nephropathy (kidney failure). This research is reported in the January issue of the journal Diabetes.

Using DNA samples from 1,362 people with Type 1 diabetes, scientists examined 1,411 patterns of common genetic differences in 212 candidate genes to detect one of the genetic contributions to the disease. As scientists obtained DNA samples from a clinical trial that has spanned more than two decades, additional invaluable information such as patients’ blood glucose levels, blood pressure rates, and lipid levels was also considered.

“By including these covariates and the time it took patients to develop complications, we were able to isolate this genetic effect,” says Dr. Andrew Paterson, SickKids scientist, Canada Research Chair in Genetics of Complex Diseases, and lead author of the study. “All diabetics are at risk of developing kidney disease. By examining all of the observations and trying to predict how quickly patients would develop complications, we were able to find the variation in the gene.”

SOD1 plays an important role in taking oxygen free radicals out of the cell and converting them into harmless products. Paterson and his colleagues believe that a variation in SOD1 influences how well the protein achieves this reaction. By enhancing function of this protein or getting rid of oxygen free radicals via another pathway, new treatments could be developed that could delay or possibly prevent the development of diabetes related complications.

Moving forward, Paterson and his colleagues aim to determine if a common genetic mechanism is involved in other debilitating, diabetes-related complications such as eye and nerve disease. While this study examined 1,411 variations, the team recently acquired data on one million variations, which they are viewing with great interest.

“This is an exciting time in human genetics,” continues Paterson. “Advances in computational technology have enabled us to measure hundreds of thousands of genetic variations in a DNA sequence, in a single reaction, and at a low cost. This has allowed us to do experiments we wouldn’t have dreamed of five years ago.” Resources, such as the International HapMap Project, a database that charts the more than three million genetic variations across the human genome and makes them freely accessible to the scientific community, aided in this study and are bolstering efforts worldwide.

Paterson also notes that diabetics who develop kidney disease are at greater risk of developing heart disease and stroke, making this type of research crucial. “The highest cost associated with diabetes comes from the screening, prevention, and treatment of related complications, not from insulin and syringes. New scientific discoveries and related treatments could have important implications for finite health care resources and could help diabetics remain active and productive members of society.”

Paterson also credits the team’s interdisciplinary approach as key to its success. “By bringing together a clinician to advise on the diabetes-related complications, a geneticist to examine the genetic variations and a mathematician to advise on the statistical analysis, we were able to focus on the problem from the various avenues required. Research into complex diseases demands collaboration and a range of expertise.”

The research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the Juvenile Diabetes Research Foundation, and the Canadian Network of Centres of Excellence in Mathematics.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

For more information, please contact:

Media Contact
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The Hospital for Sick Children
Phone: 416-813-6380
Fax: 416-813-5328