Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find major susceptibility genes for Crohn's disease

17.04.2007
Discoveries reveal new genetic risk factors for the millions of people with inflammatory bowel diseases

A consortium of Canadian and American researchers led by Dr. John D. Rioux, PhD, Associate Professor of Medicine at the Montreal Heart Institute and the Université de Montréal, report in the April 15 online edition of Nature Genetics the results from a search of the entire human genome for genetic risk factors leading to the development of Crohn's disease. Specifically, using a novel approach, the authors identified that the PHOX2B, NCF4 and ATG16L1 genes constitute genetic risk factors for Crohn's disease. In addition, their study identified two regions of the genome where genetic risk factors are located but no known genes were implicated – further work will be necessary to identify the causal genes in these regions.

More than 1 million Americans and some 170,000 Canadians have Crohn's or colitis, known collectively as inflammatory bowel disease (IBD). 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. In addition to the Montreal Heart Institute and Université de Montréal, the Consortium's member institutions include the Cedars-Sinai Medical Center in Los Angeles, the University of Chicago, the Johns Hopkins University, the University of Pittsburgh, the University of Toronto, and Yale University.

Because IBD tends to run in families and is more frequent 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 the entire genetic component of disease. To identify additional genes that are associated with IBD, the international team of researchers scanned the genome—all of 22,000 or so genes— by testing more than 300,000 single nucleotide polymorphisms, or SNPs, in people with Crohn's disease and in healthy controls. The comparison of these SNPs (common genetic variants) between patient and control groups identified multiple SNPs that were strongly associated with Crohn's disease. These findings were then tested in two additional sets of patients and healthy controls in order to confirm their results.

... more about:
»ATG16L1 »Component »Crohn' »IBD »SNP

According to the corresponding author John D. Rioux, the findings highlight numerous biological pathways not previously thought to play a role in Crohn's disease. "The identification of the PHOX2B gene in this study, for example, may implicate a role for neuroendocrine cells of the intestinal epithelium as having a role to play in Crohn's Disease. In addition, the identification of the NCF4 gene indicates that altered reactive oxygen species (ROS) production, important in the generation of an effective anti-microbial response, may lead to increased risk to developing Crohn's disease". The fact that the authors also found strong association of the ATG16L1 gene provides further evidence that an individual's response to microbes has an influence on susceptibility to Crohn's disease.

Specifically, in addition to demonstrating its association to disease, these authors have shown that ATG16L1 is essential for the normal autophagic process used to degrade worn-out cellular components and help eliminate some pathogenic bacteria. "We propose that genetic variation in the ATG16L1 gene leads to alterations in how the body uses autophagy and therefore may result in increased persistence of both cellular and bacterial components, leading to inappropriate immune activation and increased risk of Crohn's disease" adds Dr. Rioux.

The findings reported in this study are expected to not only improve on the biological understanding of disease but should also have a long-term impact on clinical practice. According to Dr. Edmond-Jean Bernard, co-author and gastroenterologist at the Hotel Dieu Hospital in Montreal and the Université de Montréal "the multiple genetic risk factors we've identified provide important molecular targets for current functional studies aimed at understanding the disease and important targets for drug development to improve therapy of Crohn's disease in the future." Dr. Stephen P. James, M.D., director of the Division of Digestive Diseases and Nutrition at the National Institutes of Health's NIDDK continued by saying that "these important discoveries not only offer new hope for better therapies for patients with Crohn's disease, they also highlight 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".

Sophie Langlois | EurekAlert!
Further information:
http://www.umontreal.ca

Further reports about: ATG16L1 Component Crohn' IBD SNP

More articles from Life Sciences:

nachricht Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie

nachricht Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>