Three new studies on the search for genetic susceptibility factors for chronic inflammatory diseases of the intestine have just been published in the December issue of Nature Genetics. In one of these, researchers analyzed the genomes of over 7,000 Europeans, around 2,300 of whom suffered from UC. Results obtained enabled identifying three new genetic susceptibility factors potentially implicated in UC: genes HNF4A, CDH1 and LAMB1.

The interest of this work lies in the fact that, for the first time, the identified genes are implicated in the elaboration and function of the intestinal epithelial barrier. Moreover, one of the new genetic susceptibility variants also seems to be strongly associated with the risk of developing colorectal cancer. Earlier studies had identified these three genes as being less strongly expressed in the intestine of patients with UC, thereby reinforcing the hypothesis of the rupture of the intestinal barrier as an early, critical event in the physiopathology of UC. Further studies focusing on the role of the intestinal epithelium are now necessary in order to propose therapeutic strategies for reinforcing this intestinal barrier effect.

Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. The UK IBD Genetics Consortium & the Wellcome Trust Case Control Consortium 2