Advances and Perspectives in the Genetics of Inflammatory Bowel Diseases

Several clinical and biological phenotypes define complex diseases such as inflammatory bowel disease (IBD). There is a critical role of the caspase recruitment domain protein 15/nucleotide-binding oligomerization protein 2–dependent (CARD15-NOD2) sensing of bacterial cell wall components in health and disease. The current etiologic model for IBD emphasizes an interaction between susceptibility and modifier genes along with environmental factors. Together, these lead to disease progression. However, further work should clarify the pathophysiological mechanisms leading to IBD and how innate immune signaling confers susceptibility to intestinal inflammation. This is a prerequisite for rational clinical management of IBD. Genetic, functional, serologic testing and development of therapeutics in IBD are discussed.

Abbreviations used in this paper:  CARD, caspase recruitment domain , CD, Crohn’s disease , DLG5, disc large homolog 5 , IBD, inflammatory bowel disease , LRR, leucine-rich repeat , NOD-LRR protein, LRR-containing nucleotide-binding oligomerization domain protein , MDP, muramyl dipeptide , MDR1, multidrug resistance 1 , NF-κB, nuclear factor-κB , NOD2, nucleotide-binding oligomerization protein 2 , PRM, pathogen-recognition molecule , PGN, peptidoglycan , SLC22A4/A5, solute carrier family 22A4/22A5 , TLRs, Toll-like receptors , UC, ulcerative colitis