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Contenu archivé le 2024-05-14

Analysis of genetic susceptibility to inflammatory bowel disease in Europe


Inflammatory bowel diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC) are common diseases occurring in young adults. They are frequently complicated by denutrition, mutilating surgery and cancerisation of the chronic inflammatory lesions. In the absence of known aetiology, their treatment is symptomatic, based on surgery, anti-inflammatory drugs and immunosupressor agents. However, these therapies are limited by their major side effects.

A genetic predisposition to IBD, compatible with a multifactorial model of inheritance, is well established and a genome-wide search, in order to localise predisposing genes for IBD, was recently initiated in Europe. It enabled the provisional assignment of linkage to the pericentromeric region of chromosome 16 of a first CD susceptibility locus named IBD1.

The identification of IBD susceptibility genes would be a key step in the understanding of the fundamental causes playing an etiologic role in IBD. However, for diseases with a complex mode of inheritance, a large number of families is required for such genetic studies. They cannot be found in a single European country. A collaborative network in order to recruit and characterise a large number of IBD families is a necessary prerequisite.

The major goals of this project are to foster the interaction of fundamental and clinical research around the genetics of IBD and to provide a powerful tool for researchers in establishing centralised clinical and biological databases of IBD families. The objectives will be reached under the following interrelated tasks: (i) the identification and recruitment of IBD families using harmonised criteria, (ii) the creation of a centralised computer database containing clinical data and the development of a repository of biological material from IBD patients, (iii) the information on genetics of IBD and promotion of genetic studies.

The recruitment of multiplex IBD families will help to reach the following objectives: 1) to localise more precisely the susceptibility gene within chromosome 16; 2) to identify additional susceptibility loci; 3) to investigate which, if any, loci involved in CD may also be relevant to UC; 4) to establish a more precise genetic model for the genetic susceptibility to IBD which would take into account the contribution of each identified locus and their possible interactions; 5) to estimate the relative risk of the different combinations of the predisposing alleles.

It is expected that our knowledge concerning the genetics of IBD will further help to provide the bases for new development including the research and the validation of molecular diagnostic tools, the identification of defined subgroups of patients who could benefit of specific treatment or could be targeted for preventive actions, the understanding of the pathophysiology of the disease and the development of new approaches for therapeutic research.

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