Current Concepts on the Genetics and Pharmacogenetics of Inflammatory Bowel Disease: Do they Help in Clinical Management?

Peter      Laszlo Lakatos; Laszlo      Lakatos

Abstract

The pathogenesis of inflammatory bowel disease is only partially understood; various environmental and host (e.g. genetic-, epithelial-, immune and non-immune) factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity. Much of the recent emphasis in inflammatory bowel disease genetics research has been directed at the evaluation of candidate disease susceptibility genes within inflammatory bowel disease linkage intervals. Such studies have elucidated associations of numerous gene variants (e.g. NOD2/CARD15, SLC22A4/A5 and DLG5) with inflammatory bowel disease, but most of these require further replication and functional validation. Some genes are associated with inflammatory bowel disease itself, while others increase the risk of ulcerative colitis or Crohns disease or are associated with disease location and/or behaviour. Recently, some new data also indicated at a possible role for genetics in predicting therapeutic success (e.g. response to infliximab or steroids). Genetic information acquired in recent years helps in understanding the pathogenesis of inflammatory bowel disease and identifying a number of potential targets for therapeutic intervention. In the future, genetics may also help in more accurate diagnosis and prediction of disease course and response to therapy in inflammatory bowel disease.

Keywords: Inflammatory bowel disease, ulcerative colitis, Crohn's disease, thiopathogenesis, genetics, NOD2/CARD15, SLC22A4/A5, DLG5