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Hundreds of identified genes involved in the pathophysiology of inflammatory bowel disease


Exemplary colonoscopy images of a non-inflamed normal control (top left panel), and that of highly inflamed Crohn Disease (CD) (top middle panel) and ulcerative colitis (UC) patients (top right panel). (Photo: Costello et al.)
Click here for full-size image.

In a paper published in PLoS Medicine researchers from the German Genome Research Network have analysed the expression of thousands of genes from patients with inflammatory bowel disease (ulcerative colitis and Crohn disease) using a genome wide approach to produce a comprehensive picture of which genes are activated in these conditions.

Using microarrays¡Xa technique in which thousands of markers for genes are placed together on a silicon chip¡Xthe researchers led by Stefan Schreiber were able to assess whether genes from patients with these two diseases were switched on or off in samples taken from the affected gut. What they found was that 650 genes differed in how active they were between normal individuals and patients with either of the diseases. Interestingly, down-regulation leading to a lack of function was the prevailing pattern the researchers found. In Crohn disease, approximately 84% of differentially expressed genes were found to be less active compared with 42% of the differentially expressed genes in ulcerative colitis. However, none of the 122 differentially expressed genes in Crohn Disease and ulcerative colitis was overexpressed in one disease and underexpressed in the other, which supports the idea of a shared underlying inflammatory process going on in both diseases. This notion is also supported by recent clinical developments that demonstrate that therapies are often applicable to both diseases.

In a second part of the study, the team looked closely at what patterns of gene expression there were; they found that there were changes in many genes associated with abnormal immune response in both diseases; and in ulcerative colitis they found changes in genes responsible for cell growth and proliferation.

Ulcerative colitis and Crohn disease are common chronic relapsing diseases; in the UK, for example, together they affect about one person in every 400, amounting to a total of 120,000 cases of ulcerative colitis and 60,000 of Crohn disease, with 6,000 new cases of ulcerative colitis and 3,000 new cases of Crohn disease every year. Current estimates are of more than 1 million cases each in the US and Europe.

This study highlights how complex the underlying disease process is in these two diseases, but also indicates some possible future avenues for research of such diseases in general.


Citation: Costello CM, Mah N, Hasler R, Rosenstiel P, Waetzig GH, et al. (2005) Dissection of the inflammatory bowel disease transcrptome using genome-wide cDNA microarrays. PLoS Med 2(8): e199.

Stefan Schreiber
University Hospital Schleswig Holstein
Christian-Albrechts University of Kiel
Schitenhelmstrasse 12
Kiel, Germany 24105
+49-431-597-1434 (fax)


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