A major step forward in the research of Crohn’s disease

Kiel, 22 November 2010 According to a new genetic study, the number of genes that are associated with Crohn’s disease can now be doubled. Altogether, there are now 71 different genes known to be triggers for this chronic inflammatory bowel disease, which are more than have been identified for any other disease so far. These findings are now available on the website of Nature Genetics (http://www.nature.com/ng/index.html). They result from the world’s largest genetic study of inflammatory bowel diseases, which took place from May 2008 to November 2010, in which more than 22,000 patients and 50 research teams in 15 countries participated. Leading the study was the “International IBD Genetics Consortium” (IIBDGC) that was headed by Professor Andre Franke of the Inflammation Research Excellence Cluster (Institute of Clinical Molecular Biology) in Kiel, Germany.

Professor Franke: “The key to finally being able to combat Crohn’s disease can be found in each of the genes. When we find that certain genetic deviation that increases the risk of Crohn’s disease, we can attempt to combat it with targeted pharmaceuticals. The goal is to manipulate the deviations – i.e. to block or deactivate them – in order to find out whether they promote the outbreak of the intestinal inflammation. Ultimately, we seek a strategy that can prevent the onset of the disease.”

“We already know that there is an interaction between these abnormal genes and external triggers, which is responsible for Crohn’s disease. About 50 percent of the disease risk is genetic. The other half is dependent on environmental factors such as smoking. The findings provide us with more information about these potential triggers and set the parameters for further research,” he continued.

The relationship between virus infection and Crohn’s disease discovered

With the study, the connection between a virus infection and Crohn’s disease was made for the first time. A known mutation in the gene called FUT2 leads to a decreased immune response against noroviruses. Exactly this mutation was also identified in the Kiel study as a further cause of Crohn’s disease.

Through the analysis of six genome-wide association studies, the researchers identified 39 previously unknown disease regions in the genetic material of the human body, which contain various genes that are associated with Crohn’s disease. Prior to this, only 32 of these regions were known. With the findings from this study, there is now a total of 71 identified disease regions.  

The background of Crohn’s disease

In western industrialized countries, about 100 per 100,000 inhabitants are affected, with increasing tendency. Most patients fall ill between the ages of 18 and 30 with inflammations of the gastrointestinal tract, which cause severe pain, weight loss, vomiting and diarrhea. Although many people come to terms with the disease through medical treatment and a controlled diet, in the long term three-quarters of the patients are surgically treated and parts of the intestines are removed due to complications in the course of the disease. All available therapies have so far only combated the symptoms of inflammation in the disease, but not the underlying causes of Crohn’s disease.

Conducting the study and future prospects

A majority of the samples were analysed in the Kiel laboratories of the Institute of Clinical Molecular Biology by David Ellinghaus, a doctoral candidate on Professor Franke’s team. David Ellinghaus reports: “In recent years it has become increasingly easier to examine millions of positions in the human genetic material, which differ among different individuals. And when you collaborate internationally and thus combine large data sets – you also find more and more causes of disease, as occurred in this study.”

The Kiel researchers and the international consortium can’t just sit back just now because, as the researchers of the current study found out, even with the 71 genes, barely 25 percent of the genetic causes of Crohn’s disease have been explained. “As of now, we will be using even more advanced technologies, such as decipering the entire genetic material of patients – the so-called "complete genome sequencing" – in search of the remaining 75 percent. With the construction of the Center for Molecular Biosciences on the former parking lot of Kiel’s new botanical garden, we will also have the necessary infrastructure.” – Professor Franke. The study was funded by the National Genome Research Network (NGFN).

EVENT ANNOUNCEMENT: Professor Franke will be presenting the study at the Third Annual Meeting of NGFNPlus and NGFN-Transfer in a lecture. Date: 26 November 2010, beginning at 12.00 noon. Location: Henry Ford Building of the Free University of Berlin, Garystr. 35, 14195 Berlin-Dahlem, Germany.

The Cluster of Excellence "Inflammation at Interfaces"

The Inflammation Research Excellence Cluster follows a unique, interdisciplinary research approach in order to decode the causes of chonic inflammation and to develop therapies for healing. The research association brings together the competences of approximately200 geneticists, biologists, nutritionists and physicians from Kiel University and the University of Lübeck, the Research Institute Borstel and the Max Planck Institute for Evolutionary Biology, Plön. In Germany alone, millions of people suffer from chronic inflammation of the lungs (asthma), the skin (psoriasis), the intestines (Crohn’s disease) and the brain (Parkinson’s disease). The trigger is a disorder of the immune system: it incessantly activates inflammatory mediators and defense cells, thereby destroying healthy tissue. The number of sufferers increases daily. This phenomenon of modern civilization has become the challenge for 21st Century medicine. Accordingly, in 2007 the German Federal Government and the German Research Foundation declared the decoding of the complex inflammation mechanism to be a national scientific priority.

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