Crohn's disease causes severe inflammation of the digestive system, with potentially serious complications. Although scientists know that some people inherit Crohn's disease, no single gene causes the disease. Crohn's disease is complex, meaning that many different genes contribute small effects that increase the likelihood of developing the disease. Environmental variables can also interact with genes to influence the risk. At this stage, scientists continue to try to identify the genes that play a role in inherited Crohn's disease.
NOD2 Gene
According to MayoClinic.com, patients with Crohn's disease are more likely to have a mutation in the NOD2 gene than healthy people. The NOD2 gene, also known as CARD15, lies on the long arm of chromosome 16. In one study described by Online Mendelian Inheritance in Man, half of the patients with Crohn's disease had an alteration in the NOD2 gene that could contribute to the disease. Compared to patients with normal copies of NOD2, patients with two faulty copies of NOD2 were younger at the time of diagnosis and were more likely to suffer from strictures, a narrowing of the intestines that blocks the flow of food through the digestive tract. MayoClinic.com adds that patients with NOD2 mutations are more likely to need surgery than patients who do not have the mutation.
Other Genes
In addition to the NOD2 gene, Online Mendelian Inheritance in Man (CE- IBD1 ref) lists 11 other genes in eight different chromosomal locations that have been tentatively associated with Crohn's disease. For each of these genes, at least one study suggests that mutation increases the risk for developing Crohn's disease. The candidate genes and chromosomal locations include: the ATG16L1 gene on the long arm of chromosome 2; MST1 or BSN on the short arm of chromosome 3; TNFSF15 on the long arm of chromosome 9; IL23R on the short arm of chromosome 1; IL10 on the long arm of chromosome 1; IL10RB on the long arm of chromosome 21; IL10RA on the long arm of chromsome 11; and MUC3A, ABCB1 and IRF5 on the long arm of chromosome 7. With the exception of MUC3A, BSN and ABCB1, all of these genes clearly function in the immune response. The strongest candidates are ATG16L1 and IL23R because several studies of patients with Crohn's disease independently identified them as risk factors.
Chromosomal Regions
In addition to the candidates cited above, Online Mendelian Inheritance in Man lists 14 other chromosomal regions that have been tentatively associated with Crohn's disease. For the other chromosomal regions, scientists do not have a good idea of which of hundreds of potential genes in the area could increase the risk of Crohn's disease. Scientists continue to follow up on these findings to identify any causative genes and determine the strength of their effects.
