page_title: Crohn's disease
section_title: Genetics
hierarchical_section_title: Crohn's disease / Causes / Genetics
caption_attribution_description: English: NOD2 protein model and schematic diagram. Two N-terminal CARD domains (red) connected via helical linker (blue) with central NOD domain (green). At C-terminus LRR domain (cyan) is located
context_page_description: Crohn's disease is a type of inflammatory bowel disease that may affect any segment of the gastrointestinal tract from the mouth to the anus. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Other complications outside the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and tiredness. The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum. Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer.
  While the causes of Crohn's disease are unknown, it is believed to be caused by a combination of environmental, immune, and bacterial factors in genetically susceptible individuals. It results in a chronic inflammatory disorder, in which the body's immune system attacks the gastrointestinal tract, possibly targeting microbial antigens. While Crohn's is an immune-related disease, it does not appear to be an autoimmune disease. The exact underlying immune problem is not clear; however, it may be an immunodeficiency state.
context_section_description: Crohn's has a genetic component. Because of this, siblings of known people with Crohn's are 30 times more likely to develop Crohn's than the general population.
  The first mutation found to be associated with Crohn's was a frameshift in the NOD2 gene (also known as the CARD15 gene), followed by the discovery of point mutations. Over 30 genes have been associated with Crohn's; a biological function is known for most of them. For example, one association is with mutations in the XBP1 gene, which is involved in the unfolded protein response pathway of the endoplasmic reticulum. The gene variants of NOD2/CARD15 seem to be related with small-bowel involvement. Other well documented genes which increase the risk of developing Crohn disease are ATG16L1, IL23R, IRGM, and SLC11A1.
  There is considerable overlap between susceptibility loci for IBD and mycobacterial infections. Genome-wide association studies have shown that Crohn's disease is genetically linked to coeliac disease.
  Crohn's has been linked to the gene LRRK2 with one variant potentially increasing the risk of developing the disease by 70%, while another lowers it by 25%. The gene is responsible for making a protein, which collects and eliminates waste product in cells, and is also associated with Parkinson's disease.
caption: NOD2 protein model with schematic diagram. Two N-terminal CARD domains (red) connected via helical linker (blue) with central NBD domain (green). At C-terminus LRR domain (cyan) is located. Additionally, some mutations which are associated with certain disease patterns in Crohn's disease are marked in red wire representation.[71]
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