A gene that promotes inflammation also plays a key role in causing Crohn's disease and ulcerative colitis - a finding that could lead to new treatments for these debilitating gastrointestinal illnesses, an international team of scientists reported Thursday.
The researchers found that the gene -- called IL-23R -- was strongly associated with an increased risk of developing chronic disorders known collectively as inflammatory bowel disease, according to a study published yesterday in the online journal Science Express.
"Knowledge of these genetic factors and our future understanding of what they do show promise for allowing us to develop more specific, targeted therapies for patients with inflammatory bowel disease," said Dr. Richard Duerr, the study's lead author and associate professor of medicine and human genetics at the University of Pittsburgh.
Inflammatory bowel disease, or IBD, affects more than 1 million Americans, causing abdominal pain, diarrhea and rectal bleeding.
"I was having a lot of diarrhea and didn't think it was anything serious," said speech therapist Lea Uhl, 28, of South Park, whose younger brother also suffers from the disease. "But then I had a colonoscopy, and they diagnosed me with Crohn's."
Scientists believe IBD develops when the immune system attacks helpful bacteria in the digestive tract, said study co-author Dr. Miguel Regueiro, a Pitt gastroenterologist.
They have long suspected that genes are involved in triggering this autoimmune response because IBD runs in families and is seen more frequently in certain ethnic groups such as Ashkenazi Jews.
Earlier studies found a link between Crohn's disease and mutations in a gene called CARD15, but that alone could not explain the genetic basis of IBD, Duerr said.
Duerr, Regueiro and the other members of the Inflammatory Bowel Disease Genetics Consortium -- consisting of eight institutions, including Pitt -- set out to identify other genes associated with IBD. The consortium is funded by the National Institute of Diabetes and Digestive and Kidney Diseases.
They tested more than 300,000 genetic markers in more than 550 people with Crohn's disease and an equal number of healthy people. They found three markers strongly associated with Crohn's disease -- two in the CARD15 gene and a third on the IL-23R gene.
The IL-23R gene stores the information for an immune system molecule called interleukin-23, which regulates inflammation and helps fight infection.
The researchers discovered that one version of this gene increased risk for developing IBD. They also found a rare mutation in IL-23R that provided protection, said Duerr, whose research was financed in part with a grant from the Scaife Family Foundation.
How exactly the IL-23R gene works remains unclear.
By trying to mimic the protective version of the gene -- or blocking the variant that increases susceptibility to IBD -- scientists might be able to develop better drugs, said Dr. Jay Kolls of Children's Hospital of Pittsburgh, who studies the role of IL-23 in cystic fibrosis, but was not involved in consortium research.
"These data really support the contention that this molecule is a good target in trying to treat inflammatory bowel disease," Kolls said.
Experts say current treatments for IBD such as anti-inflammatory drugs, steroids and antibiotics are inadequate.
"This is one of the desperate areas in medicine where our therapies have improved in the past several years, but we still have a very long way to go," Regueiro said.
An early-stage clinical trial sponsored by Centocor Inc. in Montgomery County found IBD patients improved when given an antibody that blocks IL-23.
"It would be fabulous to be able to live your life without worrying, without always having to know where the bathroom is no matter where you are," Uhl said.
