Cedars-Sinai researchers on multicenter team linking gene mutation to Crohn's disease

LOS ANGELES (EMBARGOED UNTIL OCT. 26, 2006 AT 2 P.M. ET) -- The North American IBD Genetics Consortium has linked a gene mutation to the development of Crohn's disease, a chronic, relapsing inflammatory disorder of the gastrointestinal tract that affects 100 to 150 of every 100,000 people of European ancestry. The consortium is composed of IBD genetics research groups from seven centers in North America, including Cedars-Sinai Medical Center, and this effort was led by teams at Yale University and the University of Pittsburgh.

"Crohn's disease and other inflammatory bowel diseases often elude diagnosis for many years while patients suffer and physicians search for clues. The identification of defective genes helps physicians provide early identification of people who are at risk for Crohn's disease and enables pharmaceutical companies to develop targeted drug therapies," said Jerome I. Rotter, M.D., one of several researchers at Cedars-Sinai Medical Center participating in the study. He is director of Research and co-director of the Medical Genetics Institute, and director of the Division of Medical Genetics at Cedars-Sinai.

"The discovery of genetic mutations also may lead to improved research methods and the development of gene therapies targeting Crohn's disease, ulcerative colitis and other inflammatory disorders," Rotter said.

The multicenter research team confirmed the involvement of one gene, called Nod2 or CARD15, and discovered that a defect of the interleukin-23 receptor gene (IL-23R) also led to the development of Crohn's disease.

"Inflammatory bowel disease is an umbrella term that includes a variety of disorders. The more specific we can be in diagnosing a particular disease, the more specific we can be in prescribing an appropriate therapy," said Stephan R. Targan, M.D., director of both the Inflammatory Bowel Disease Center and the Division of Gastroenterology at Cedars-Sinai.

Interleukin-23 is a molecule that enables cells to signal to each other and is also a very precise regulator of parts of the immune system, according to Kent D. Taylor, Ph.D., second author on the study and a research scientist in Cedars-Sinai's Medical Genetics Institute, along with Huiying Yang, Ph.D. The IL-23R gene provides the genetic code for the cell receptor, which is located on the outside surface of a cell. IL-23 binds to the IL-23 receptor to provide instructions for the cell. It is this point in the signaling pathway that has now been implicated in the development of Crohn's disease.

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The study's authors represent the IBD Genetics Consortium, which is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health. The Consortium's member institutions include Cedars-Sinai Medical Center, the University of Chicago, Johns Hopkins University, Université de Montréal, the University of Pittsburgh, Mount Sinai Hospital in Toronto and the University of Toronto, and Yale University.

Senior author of the paper is Judy H. Cho, M.D., associate professor in the departments of medicine and genetics at Yale School of Medicine. Richard H. Duerr, M.D., associate professor of medicine and human genetics at the University of Pittsburgh, is the first author. In addition to the Cedars-Sinai researchers, authors contributing to the paper include: Steven R. Brant, M.D., Themistocles Dassopoulos, M.D., and Lisa Wu Datta, M.S., Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center and the Johns Hopkins University Bloomberg School of Public Health, Baltimore; John D. Rioux, Ph.D., Université de Montréal and the Montreal Heart Institute, Montreal; Mark S. Silverberg, M.D., Ph.D., and A. Hillary Steinhart, M.D., Mount Sinai Hospital IBD Centre, University of Toronto; Mark J. Daly, Ph.D., Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston; Clara Abraham, M.D., Emily O. Kistner, Ph.D., L. Philip Schumm, M.A., and Dan L. Nicolae, Ph.D., University of Chicago; Miguel Regueiro, M.D., University of Pittsburgh School of Medicine; Anne Griffiths, M.D., Department of Pediatrics, The Hospital for Sick Children, Toronto; Alain Bitton, M.D., Royal Victoria Hospital, McGill University Health Centre, Montreal; Annette Lee, Ph.D., and Peter K. Gregersen, M.D., Feinstein Institute for Medical Research, Manhasset, N.Y.; and M. Michael Barmada, Ph.D., University of Pittsburgh Graduate School of Public Health.

The Medical Genetics Institute of Cedars-Sinai Medical Center is part of the Burns and Allen Research Institute, one of the largest, hospital-affiliated research centers on the West Coast. In addition to research on inflammatory bowel disease, research at the Medical Genetics Institute of Cedars-Sinai Medical Center includes studies of type 2 diabetes, retinopathy, coronary artery disease, insulin resistance and hypertension in Mexican-Americans from Los Angeles, skeletal dysplasias, mitochondrial disorders and neurogenerative disorders.

One of seven hospitals in California whose nurses have been honored with the prestigious Magnet designation, Cedars-Sinai Medical Center is one of the largest nonprofit academic medical centers in the Western United States. For 18 consecutive years, it has been named Los Angeles' most preferred hospital for all health needs in an independent survey of area residents. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities and is fully accredited by the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP). Additional information is available at www.cedars-sinai.edu.

Citation: Science, published online on Oct. 26, 2006 at Science Express, "Association of the interleukin-23 receptor with Crohn's disease and ulcerative colitis"


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