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The Children's Hospital of Philadelphia: New Gene-Searching Method Uncovers Possible New Targets for Crohn's Disease Drugs
Date:2/26/2009

analytic equipment to sweep through the full range of all 23 human chromosomes and detect the most significant gene variants associated with a given disease. Those variants, each a change in a single DNA base, are called single nucleotide polymorphisms (SNPs).

However, individual GWA studies often do not have the statistical power to detect subtle but important variants that are involved in disease development. By using an algorithm developed by Kai Wang, Ph.D., at the Center for Applied Genomics, Hakonarson's study team created a pathway-based approach that seeks out interacting or related genes along the same biological pathway. "We applied our pathway-based approach to GWA data for Crohn's disease, but conducted the search without starting with a hypothesis focused on a specific suspected pathway," said Hakonarson. "Among hundreds of known biological pathways, the one that surfaced from the analysis as being most significant included genes already known to be relevant to the biology of Crohn's disease."

That pathway, the interleukin 12 (IL12) pathway, governs cell receptors involved in the development of Crohn's disease. Hakonarson added that the IL12 pathway might be more correctly referred to as the IL12/IL23 pathway, since IL12 receptor signaling converges with signaling on another receptor, IL23. Previous work by other researchers had shown that monoclonal antibodies that block the IL12 or IL23 receptor show some clinical success in treating Crohn's disease.

"As we better understand the gene pathways operating in Crohn's disease, we are uncovering more potential targets for effective drug treatments," said pediatric gastroenterologist Robert Baldassano, M.D., a study co-author and the director of the Center for Pediatric Inflammatory Bowel Disease at Children's Hospital. He added that developing targeted therapies based on gene pathways might allow doctors to tailor treatments to a patient's genetic profile.
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SOURCE The Children's Hospital of Philadelphia
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