Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

McGill researchers discover gene that increases susceptibility to Crohn's disease

13.01.2009
'Broken' bacterial sensor doesn’t detect harmful bacteria in the digestive system

Researchers at McGill University, the Research Institute of the McGill University Health Centre (RI MUHC) and the McGill University and Génome Québec Innovation Centre, along with colleagues at other Canadian and Belgian institutions, have discovered DNA variations in a gene that increases susceptibility to developing Crohn's disease. Their study was published in the January issue of the journal Nature Genetics.

The study was led by McGill PhD candidate Alexandra-Chloé Villani under the supervision of Dr. Denis Franchimont and Dr. Thomas Hudson. Dr. Franchimont, now with the Erasme Hospital in Brussels, Belgium, was a Canada Research Chair formerly affiliated with the Gastroenterology Dept. of the MUHC. Dr. Hudson, former Director of the McGill University and Génome Québec Innovation Centre, is now the President and Scientific Director of the Ontario Institute for Cancer Research (OICR), located in Toronto.

The researchers pinpointed DNA sequence variants in a gene region called NLRP3 that are associated with increased susceptibility to Crohn's disease. Crohn's is a chronic relapsing inflammatory disease of the digestive system that can affect any part of the gastrointestinal tract. Patients can suffer from a number of different symptoms in various combinations, including abdominal pain, bloody diarrhea, fever, vomiting and weight loss. Rarer complications include skin manifestations, arthritis and eye inflammation.

"Although the exact cause of Crohn's disease is still unknown, both environmental and genetic factors are known to play a critical role in the pathogenesis of the disease," Dr. Franchimont said.

Crohn's disease is found throughout the world. However, it appears to be most common in North America and northern Europe, and Canada has one of the highest incidence rates in the world. Crohn's affects between 400,000 and 600,000 people in North America.

The 400 square metres of the intestinal absorptive area is the largest single surface in or on the human body, and it is covered by billions of bacteria of the intestinal microflora living in the gastrointestinal tract.

"The single layer of cells lining your intestinal digestive tract is thus constantly exposed to high levels of bacteria and pathogens," Villani explained. "These cells must recognize and respond appropriately to the harmful bacteria while maintaining tolerance to the non-pathogenic 'good' bacteria that make up your intestinal microbial flora. This is the central challenge of the digestive immune system, which needs to balance defence versus tolerance."

"The protein encoded by the Crohn's disease susceptibility gene NLRP3, cryopyrin, is an intracellular bacteria sensor that plays a key role in initiating immune response," explained Villani. Based on their results, researchers theorize the bacterial sensor cryopyrin is probably defective in some patients, and doesn't correctly recognize the presence of harmful bacteria.

"When the digestive immune system's counter-attack is insufficient to clear the threat," Ms. Villani continued, "there is a bacterial infiltration in the intestinal wall through the first line of defence mechanisms. The digestive immune system will again try to repel the threat, but the effort may not be sufficient, and this usually leads to a vicious cycle that results in chronic inflammation in the intestinal wall. And that is Crohn's disease."

"This gene also plays a central role in the regulation of fever, which is one of the most primitive defence mechanisms that exists in humans to fight the surrounding pathogenic bacteria," Dr. Hudson added. "DNA sequence variations in the NLRP3 gene are also known to be responsible for hereditary periodic fever syndromes."

"Previously published genome-wide association studies have already detected more than 30 distinct Crohn's genetic factors, but these only explain about one-fifth of Crohn's disease heritability", said Dr. Franchimont.

Though these results will not lead to any new short-term treatments for Crohn's, Dr. Franchimont is confident that in the longer term it will benefit patient care. "Studies like this one give us a better understanding of key pathways and pathogenic mechanisms involved in Crohn's disease," he said. "Now that we are aware of the role of bacterial sensors in the disease, steps can be taken to develop a new treatment strategy."

Mark Shainblum | EurekAlert!
Further information:
http://www.mcgill.ca

More articles from Life Sciences:

nachricht Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>