Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New gene found for Crohn's disease

30.10.2006
A consortium of American and Canadian researchers report in Science Express, a rapid online publication by the journal Science, the discovery of a new genetic link to Crohn's disease. While most of the mutations in the gene, which codes for a receptor in a major inflammatory pathway, are strongly associated with Crohn's, surprisingly, one type of mutation appears to confer significant protection. The finding, say the researchers, points to a crucial target for drugs that might better manage Crohn's disease and ulcerative colitis.

More than 1 million Americans have Crohn's or colitis, known collectively as inflammatory bowel disease (IBD).

"Crohn's and colitis are chronic conditions that profoundly impact the day-to-day lives of affected individuals. Moreover, inflammatory bowel disease often runs in families, making the pinpointing of the responsible genes especially important if we are to find ways to better treat or even prevent IBD," said first author of the study, Richard H. Duerr, M.D., associate professor of medicine and human genetics at the University of Pittsburgh.

According to senior author Judy H. Cho, M.D., associate professor in the departments of medicine and genetics at Yale School of Medicine, the findings highlight a major inflammatory pathway and change in thinking about disease-associated genetic variation.

... more about:
»Associate »Crohn' »IBD »Mutation »SNP »inflammatory

"This pathway is particularly intriguing because we appear to have identified a gene variant that protects against development of IBD, a finding that may lead us to think about the genetics of health as much as about the genetics of disease," said Dr. Cho, who also is director of the Inflammatory Bowel Disease Center at Yale.

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 (NIH). In addition to the University of Pittsburgh and Yale, the consortium's member institutions include Cedars-Sinai Medical Center in Los Angeles, the University of Chicago, Johns Hopkins University, Université de Montréal, Mount Sinai Hospital in Toronto and the University of Toronto.

Because IBD tends to run in families and is more frequently seen in certain ethnic populations, especially Ashkenazi Jews, scientists have long suspected a significant genetic component. Although previous genetic studies found a link between Crohn's disease and mutations in a gene known as CARD15, those mutations alone are not considered to account for all of the genetic components of the disease.

To identify additional genes that are associated with IBD, the researchers scanned the genome--all 22,000 or so genes--by testing more than 300,000 single nucleotide polymorphisms, or SNPs, in people with Crohn's disease. For comparison, they looked for the presence of these SNPs in a similar number of people without IBD.

Out of the hundreds of thousands of SNPs, the genome-wide scan found three that were most strongly associated with Crohn's disease. Of those, two were in the CARD15 gene. However, the third SNP was located in a different gene on a different chromosome.

When the researchers looked at the specific gene where the third SNP resided, they found that it coded for a protein that is part of the immune cell receptor for interleukin-23 (IL-23), an important mediator of inflammation in the body. However, when they began looking for all of the polymorphisms in the IL-23 receptor gene of affected individuals to determine which ones were the most detrimental, they made an unexpected discovery. Although several polymorphisms were associated with a significantly increased risk of developing IBD, one appeared to confer a very strong protection against IBD.

"Of all the SNPs we studied in people with and without IBD, this protective SNP was the most statistically significant finding in our study. So, it took us a bit by surprise," said Dr. Duerr. "We are not sure yet what it means in terms of improving treatments for IBD patients. But, we speculate that blocking the activity of IL-23 or manipulating its pathway will be an effective way to manage IBD," said Dr. Duerr, who also is head of the Inflammatory Bowel Disease Genetics Program at the University of Pittsburgh School of Medicine and co-director of the Inflammatory Bowel Disease Center at the University of Pittsburgh Medical Center (UPMC).

In an early stage clinical trial led by other investigators, IBD patients given a monoclonal antibody that blocks IL-23 and a related inflammatory mediator saw their conditions improve. Furthermore, recent studies in mice in which the gene for IL-23 is deleted demonstrated that IL-23 is essential for the development and maintenance of chronic intestinal inflammation. Such evidence, combined with the current discovery, suggests therapies that target the IL-23 pathway may lead to more individualized, better-directed therapies for IBD, the authors say.

"This important discovery not only offers new hope for better therapies for patients with Crohn's disease, it also highlights 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," said Stephen P. James, M.D., director of the Division of Digestive Diseases and Nutrition at the National Institutes of Health's NIDDK.

The authors caution that more must be understood about the role the IL-23 pathway serves in protecting against other diseases before seeking to block or manipulate its activity with drugs or other means.

Lisa Rossi | EurekAlert!
Further information:
http://www.upmc.edu

Further reports about: Associate Crohn' IBD Mutation SNP inflammatory

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>