[NEWS, 15 March 2010] An international team of researchers has identified as many as 30 human genes which contribute to ulcerative colitis susceptibility. The results, which are presented in the scientific , provide a significant improvement of our understanding of the genetic contribution to chronic intestinal inflammation, and give hope for more precise diagnostics and tailor-made treatment strategies in the future.
Chronic inflammatory diseases (CIDs) comprise a class of disorders characterized by severe immune dysregulation and inflammation of otherwise healthy tissue. CIDs have a significant socio-economic impact, and affect up to 10 percent of the population in industrialized societies. It is known that many CIDs have a considerable genetic predisposition, including the Inflammatory Bowel Diseases (IBD). Crohn’s disease (CD) and Ulcerative Colitis (UC), the two major forms of IBD, manifest as chronic inflammation of the gastrointestinal tract, and recent data indicate that the gut microbiota may contribute to the perpetuation of the inflammatory process in genetically susceptible individuals.
Scanning the entire human genome for genes predisposing to CIDs is very costly and technologically demanding, and requires considerable well defined clinical material and data. In recent years, the A*STAR funded Genome Institute of Singapore (GIS) and the Karolinska Institutet (KI) have successfully collaborated and identified biomarkers for multiple CIDs including rheumatoid arthritis, psoriasis, and now ulcerative colitis.
The most recent study was lead at GIS by Drs Martin Hibbered and Mark Seielstad. Participating from Karolinska Institutet were Associate Professor Leif Törkvist, Associate Professor Mauro D’Amato and Professor Sven Pettersson. All and all over 50 researchers from Sweden, Singapore, Italy, Canada, the Netherlands and the US participated in the study.
Some of the genes we have identified are involved in the maintenance of mucosal integrity, and in specific cellular pathways that represent potential new targets for therapeutic exploitation, says Associate Professor Mauro D’Amato.
Our result highlight the need to further our understanding of gut microbiota and its role in the pathophysiology of ulcerative colitis, since many of the genes identified in this study point to the crosstalk between gut microbiota and the immune system, says Professor Sven Pettersson, scientific coordinator of Karolinska Institutet’s collaboration with Singapore.
Mark Seielstad et al.Genome-wide association identifies multiple ulcerative colitis susceptibility loci
Nature Genetics, online 14 March 2010