"We propose that genetic variation in the ATG16L1 gene leads to alterations in how the body uses autophagy and therefore may result in increased persistence of [toxic] cellular and bacterial components. This may lead to an inappropriate immune activation and increased risk of Crohn's disease," says co-author Dr. Ramnik Xavier, a gastroenterologist at the Massachusetts General Hospital's (MGH) Center for the Study of IBD and a researcher at the MGH Center for Computational and Integrative Biology.
This study's findings are expected not only to improve on the biological understanding of disease but also should have a long-term impact on clinical practice, according to Dr. Steven Brant, co-author and gastroenterologist at Johns Hopkins University.
"The multiple genetic risk factors we've identified provide important targets for current functional studies aimed at understanding the disease. These will be important targets for drug development to improve therapy of Crohn's disease in the future," he said.
Stephen P. James, M.D., director of the division of digestive diseases and nutrition at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) agreed, saying that "these important discoveries not only offer new hope for better therapies for patients with Crohn's disease, but they also highlight the promise of the human genome project and subsequent investments by the NIH in large-scale, collaborative research projects to unravel the causes of, and hopefully better treatments for complex, enigmatic diseases".
In addition to finding the additional Crohn's disease susceptibility genes, the researchers got strong signals for genetic risk factors located in areas of the genome where there are no known genes. "Further work will be n
Source:University of Pittsburgh Schools of the Health Sciences