Inflammatory bowel disease (IBD) is a polygenic disorder, as demonstrated by epidemiological evidence, genetic linkage, and the identification of the first susceptibility gene, NOD2.
Inflammatory bowel disease (IBD) is a typical example as patients with longstanding IBD are at an increased risk for developing colorectal cancer (CRC) and mutations of the NOD2/CARD15 gene increase the risk for Crohn's disease (CD).
CARD15 functions as an intracellular receptor for bacterial components and thus represents an important link between inflammatory bowel disease and innate immunity.
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a cytosolic innate immune receptor associated with inflammatory bowel disease susceptibility.
NOD2 mutations increase the susceptibility to inflammatory bowel diseases and the CD1d bound to α-galactosylceramide [α-GalCer] alleviates intestinal inflammation.
A better understanding of how host genetics, including NOD2, influence immune-microbe interactions and alter susceptibility to IBD is necessary in order to develop therapeutic and preventative treatments.
A case-control study of NOD2 polymorphisms known to be associated with Crohn's disease (CD) (Pro(268)Ser, Arg(702)Trp, Gly(908)Arg, and Leu(1007)fsinsC) was performed in 229 cases of primary AS with no diagnosed inflammatory bowel disease (IBD), 197 cases of AS associated with IBD (referred to as colitic spondylarthritis; comprising 78 with CD and 119 with ulcerative colitis [UC]), and 229 ethnically matched, healthy controls.
A consistent observation across most populations is that any of three polymorphisms of the Caspase-activated recruitment domain (CARD15) gene are more prevalent in IBD patients as compared with unaffected controls.
A major role in adult Crohn's disease (CD) has been defined for 3 polymorphisms in the CARD15 gene, whereas variants in the SLC22A4, SLC22A5, and DLG5 genes could have a minor contribution to IBD susceptibility.
A population-based case-control study was performed including 91% of all people in Canterbury, New Zealand, with inflammatory bowel disease (IBD); NOD2 genotyping was performed and patients were phenotyped according to the Vienna and Montreal classification systems.
A significant role for CARD15/NOD2 gene in predisposition to SpA was ruled out, in agreement with the hypothesis that the inflammatory bowel disease in SpA is determined by factors different than those responsible for isolated Crohn's disease.