Causes and Risks Factors of Crohn’s and Colitis
If someone has Crohn’s, their identical twin with the exact same genetics has 50% chance of developing Crohn’s .If someone has ulcerative colitis, their identical twin has 10% chance of developing colitis .Genetics, therefore, contributes to the development of IBD, but is not the sole cause.Genes that have been associated with Crohn’s and colitis include:
1) CARD15 is Associated with Crohn’s Disease
CARD15 binds to bacterial cell wall, and activates NF-kB, which then stimulates production of proinflammatory signals .CARD15 mutation results in defective innate immune response to gut bacteria, which can cause dysbiosis in IBD.
2) OCTN1 and OCTN2 are Associated with Crohn’s Disease
Two genetic mutations that in OCTN1 and OCTN2, SLC22A4 and SLC22A5, respectively, have been associated with Crohn’s disease.These mutated genes are mostly expressed in the gut lining, macrophages, and T cells, and cause decreased carnitine transport.However, there is still no direct evidence other than genetic data that demonstrate that these two genes are directly involved in the development of IBD.
3) DLG5 is Associated with Crohn’s Disease and Ulcerative Colitis
DLG5 helps maintain gut lining integrity.A mutation (G113A) of DLG5 is associated with CARD15 mutation in Crohn’s disease.
4) MDR1 (Multi Drug Resistant 1) is associated with Crohn’s and Colitis
MDR1 transports drugs and foreign substances outside of cells.MDR1 has been associated with Crohn’s and colitis (R, R).MDR1 is associated with treatment-resistant IBD.Mice without MDR1 spontaneously develop colitis.