TY - JOUR T1 - NOD2/CARD15 and the Paneth cell: another piece in the genetic jigsaw of inflammatory bowel disease JF - Gut JO - Gut SP - 1533 LP - 1535 DO - 10.1136/gut.52.11.1533 VL - 52 IS - 11 AU - M C Aldhous AU - E R Nimmo AU - J Satsangi Y1 - 2003/11/01 UR - http://gut.bmj.com/content/52/11/1533.1.abstract N2 - Expression of NOD2/CARD15 in the Paneth cell may be critical in the pathogenesis of Crohn’s disease The emergence and application of novel molecular techniques over the last decade has provided a needed catalyst to studies of the pathogenesis of the chronic inflammatory bowel diseases (IBD): Crohn’s disease (CD) and ulcerative colitis (UC). Successful development of genetically engineered models of intestinal inflammation has not only provided insight into the dysregulation of the mucosal immune system characteristic of IBD but has also emphasised the critical and complex role of the bacterial flora in establishing and maintaining chronic intestinal inflammation.1 These advances in understanding pathophysiology in turn have already led to novel therapeutic approaches.2,3 However, it is in studies of human genetics that landmark progress has been made, widely recognised not only within gastroenterology but also by investigators in all complex diseases.4 Genome wide scanning led initially to the identification of a number of susceptibility loci, the statistical evidence for which satisfy stringent criteria for definite linkage.5 The subsequent detection of the NOD2/CARD15 gene6–8 within the IBD1 linkage interval and the association of mutations within this gene with susceptibility to CD is widely regarded as the most stringent proof of principle for hypothesis free genome scanning in complex diseases. In the time that has elapsed since the discovery of NOD2/CARD15, the contribution of this gene in determining susceptibility and disease behaviour in IBD has received detailed examination. It is now clear that NOD2/CARD15 mutations are associated with susceptibility to CD but not UC.6 However, the contribution is subject to considerable ethnic and even regional variation. Whereas mutations may be carried by up to 50% of central Europeans with CD,9 these mutations are not present in Japanese10 or Afro-American11 patients. Even within Europe, … ER -