Genetic factors influencing affecting the development of IDB
Since the discovery of key areas of the IDB1 such as NOD2/ CARD15 , approximately nine distinct loci have been identified to play a role in the development of IDB. Genes associated with the development of IDB have been identified to affect bacterial recognition, immune response, mucosal transport or polarity. (Furguson et al 2007)
- Genes affecting bacterial recognition
- Autophagy-related 16 like 1 (ATG16l1)
ATG16L1 has been identified as part of the autophagosome pathway playing an important role in the processing of bacteria. - Human beta defensin B2, B3, B3
Studies have identified that patients with mutation in the CARD15 gene exhibit weaker expressions of the defensin gene.Of the most effected is the expression of human alpha defensin in the ileal Paneth cells. Individual with IDB also exhibit a reduction in the expression of Human Beta defensin within the colon, specifically the epithelial beta defensins HBD2, HBD3 and HBD4. - Caspase-activatin recruitment domain 15(CARD15)
CARD15 has been strongly associated with the development of CD. The CARD15 encodes the Nucleotide-binding oligomerization domain-containing protein (NOD2) which has been thought to protect individuals against invasive bacteria, by eliminating intracellular pathogens in the epithelial cells at the gastrointestinal mucosa barrier. CARD15 functions as sensor for the presence of peptidoglycan located in the cell walls of bacteria. CARD15 is expressed by Macrophage cells and intestinal paneth cells and is involved in modulating the activity of the immune related transcription factor, NF Beta Kappa.
CD has been linked to the pericentrometric region of chromosome 16. CARD15 acts as a susceptibility allele, with three polymorphisms R702W, G908R and 1007fs. Distinctive phenotypic associations with CD suggests that most CD patients with the CARD15 gene tend to be people of younger European descent with a family history of the disease as well as an obstructive or stenosing disease located in the ileum.
- Autophagy-related 16 like 1 (ATG16l1)
- Genes affecting Immune response
- Major Histocompatibility complex (MHC)
Studies have shown that the IBD3 locus on chromosome 6p, containing the MHC region has been associated with development of UC. - Interleukin-23 receptor(IL23R)
The IL23R gene located on chromosome region 1p31 is responsible for encoding a subunit of the receptor for IL23, a pro inflammatory cytokine.IL23 R has been associated with the development of CD - Toll-like receptor (TLRs)
Toll receptors are pattern that induce innate immune responses in antigens-presenting cells, such as dendritic cells, which themselves are linked to adaptive immune response.TLR4 located in the gut lymphoid and epithelial cells act by sensing components of the colonic microbiota and inducing innate immune responses TLR4 are located on chromosomal region 9p. TLR4 plays a role in the development of both UC and CD.
- Major Histocompatibility complex (MHC)
- Genes affecting mucosal transport
- Sodium dependent organic cation transporters (SLC22A4 and SL22A5)
SLC22A4 and SLC22A5 have been associated with the IBD5 locus responsible for the development of CD in adults. SLC22A4 and SLC22A5 genes function in the transport of 1-carnitine and elimination of cation drugs in the intestines - ATP-binding cassette subfamily B member 1 (ABCB1)
The ABCB1 gene is located at the chromosomal region7q21.1. This gene encodes for adenosine triphosphate-dependent efflux transporter pump protein.ABCB1 is highly expressed in the epithelial surface of the intestines, where it plays a role in the protection of the epithelium against xenobiotics. ABCB1 has been suggest to be involved in the development of UC. - Drosophila discs large homologue 5(DLG5)
The DLG5 gene is located on chromosome region 10q23. DLG5 is widely expressed in the small bowel, intestinal epithelial cells and colon. DLG5 has been associated with the development of Crohn's disease
- Sodium dependent organic cation transporters (SLC22A4 and SL22A5)
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