New ulcerative colitis gene found

Jul 9 2007

Researchers at The Hospital for Sick Children (SickKids), Mount Sinai Hospital and the University of Pittsburgh have identified a previously unsuspected gene found to be associated with ulcerative colitis.

This research is reported in the July 5 issue of Current Biology.

Inflammatory Bowel Disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic debilitating disease that affects the intestinal tract. The diseases can strike anyone at anytime and according to the Crohn's & Colitis Foundation of Canada, approximately 170,000 Canadian men, women and children have IBD.

The genetics and pathogenesis of Crohn's disease have been well characterized with the discovery of several susceptibility genes. However, the pathogenesis of ulcerative colitis has not been as clear.

"We found a previously unsuspected gene called (PTPRS) that expresses an enzyme called PTPsigma," said Dr. Daniela Rotin, the study's corresponding author, senior scientist in Cell Biology at the SickKids Research Institute, professor of biochemistry at the University of Toronto and Canada Research Chair in Biochemistry and Signal Transduction. "This type of protein is important for the regulation of cell growth, mammalian development and cancer."

"Using animal models as well as genetic analysis on DNA samples collected from ulcerative colitis patients and their parents, we found that the DNA from the patients encodes a specific form of this enzyme that is missing a protein segment," added Dr. Aleixo Muise, study lead author and clinical fellow in the Division of Gastroenterology at SickKids.

Drs. Rotin and Muise believe that losing this particular protein segment may contribute to the development of ulcerative colitis.

This discovery provides important and exciting insights into the pathogenesis of ulcerative colitis and may lead to improvements in both the diagnosis and treatment of patients with colitis. Furthermore, this novel model will allow researchers to better understand the underlying defects in the gut associated with ulcerative colitis.

Other researchers on this paper were Thomas Walters, Eytan Wine, Dan Turner, Bo-Yee Ngan, Anne M. Griffiths and Philip Sherman from SickKids, Richard H. Duerr and Miguel D. Regueiro of the University of Pittsburgh, Wei Xu of Princess Margaret Hospital, and Mark S. Silverberg of Mount Sinai Hospital.

This research was funded by the Canadian Institutes of Health Research, the Crohn's & Colitis Foundation of Canada, the Thrasher Foundation and SickKids Foundation.

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.