Crohn's Disease Genetics

Crohn’s disease often affects young adults, and its incidence has increased greatly over the last 50 years, probably reflecting changes in the environment and lifestyles. Possibly as a result of faulty responses to microbes living in the gut, the immune system of a patient is triggered to attack the gut lining, causing it to ulcerate and break up. Crohn’s disease has complex genetic causes, but no major gene contributing to disease susceptibility or pathology has previously been identified. One susceptibility gene was mapped in 1996 to human chromosome 16.

Now, advances in molecular genetics and the availability of the human genome sequence have led to the identification of a gene that occurs on the previously implicated region on chromosome 16. This gene is mutated in a subset of patients with Crohn’s disease.

The gene encodes a protein called Nod2. Intriguingly, Nod2 is involved in the recognition of microbes and signalling events leading to an appropriate immune response. The mutations found in patients disrupt proper signalling, which suggests a close link between the immune response to gut microbes and the development of disease.

There is no single gene for Crohn’s disease, and not every person with mutations in the gene for Nod2 will be affected. Nevertheless, Nod2 does seem normally to protect against the disease, and mutations in the gene increase disease susceptibility. Restoration of proper Nod2 function in such individuals could represent a promising preventative therapy.

CONTACT:

Dr Gilles Thomas
Fondation Jean Dausset CEPH
Paris, France
Tel +33 6 08 98 22 00
E-mail Thomas@cephb.fr

Dr Gabriel Nunez
University of Michigan Medical School
Ann Arbor, Michigan, USA
Tel +1 734 764 8514
E-mail Bclx@umich.edu

(C) Nature press release.

Message posted by: Trevor M. D'Souza