Digest This - Special Edition 2008 - (Page 11)

Digestive Disease institute iBD genetics program contributes to Discovery By the end of the year, the majority of genes that have a significant effect on causing Crohn’s disease (CD) and ulcerative colitis (UC) are expected to be identified. The Cleveland Clinic Inflammatory Bowel Disease Genetics Program was launched four years ago to gather DnA samples to investigate the genetic pathogenesis of IBD in association with environmental factors and the alterations in the function of the immune system that may lead or contribute to the development of CD and UC. In the U.S., more than 1 million people have one of these two forms of IBD. While there is no known cure, today’s medical therapies can significantly control the symptoms of IBD. The IBD genetics program involves the clinical and research work of Jean-Paul Achkar, MD, program head; Aaron Brzezinski, MD, Department of Gastroenterology and Hepatology, Bret Lashner, MD, Director of the Center for Inflammatory Bowel Disease in the Department of Gastroenterology and Hepatology and Bo Shen, MD, Department of Gastroenterology and Hepatology. To date, the program has collected more than 600 DnA samples from IBD patients and approximately 400 DnA samples from control patients. Early epidemiologic evidence regarding the role of genetic factors in the pathogenesis of IBD originates from studies that show higher rates of IBD among whites and persons of Jewish ethnicity, familial aggregation of IBD, and a higher concordance rate of both twins developing IBD in monozygotic compared to dizygotic twins. However, searching for specific IBD susceptible genes has been arduous because of the intrinsic complexity of genetics, involvement of several genes and the influence of environmental factors and the intestinal microflora, explains Dr. Achkar. What’s more, disease heterogeneity suggests that CD and UC are not single, unique diseases, but rather CD and UC consist of several different disease subtypes that share clinical features. While the list of identified IBD genes nears completion, medical scientists are beginning their research to understand the molecular mechanisms of gene abnormalities and how they function. To find the answers to key questions about gene abnormalities, the IBD genetics program is collaborating with Claudio Fiocchi, MD, Professor of Molecular Medicine, Lerner College of Medicine, and other researchers. Dr. Fiocchi notes it will take another five to 10 years of extensive testing to understand how these genetic abnormalities impact the disease development or manifestation, and to create new and specific therapeutic approaches. “We’re also focusing our work in trying to understand the clinical implications of IBD genetic abnormalities,” says Dr. Achkar. “We need to understand how these genetic abnormalities lead to the development of CD and UC in patients, which will enable us to develop new clinical therapies and to better target such treatments to specific patient subgroups.” Dr. Jean-Paul Achkar This hypothetical pedigree represents how several members of a family can be affected by IBD. Members shown in the color-filled symbols are those who have IBD. Ultimately, medical research is expected to enable physicians to know the specific genetic makeup of patients as well as the phenotypes of their IBD disease that will provide customized medical treatments, predict outcomes and risk complications, assess the need for surgery and measure responses to therapy. “For example, if we know through the genetic makeup of a patient that he or she will have an aggressive type of IBD, then the physician may take a different approach in treating it, as compared to a patient predicted to have a less aggressive type of IBD,” says Dr. Achkar. For more information, email digestthis@ccf.org clevelandclinic.org /digestthis InVESTIGATIonS {11} http://www.clevelandclinic.org/digestthis

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Digest This - Special Edition 2008 Table of Contents Investigations Institute Overview Innovations Staff Research

Digest This - Special Edition 2008

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