Crohn's disease is a lifelong, incurable disorder that is caused by inflammation of the digestive tract, and is classified as an inflammatory bowel disease. Crohn's most commonly affects the ilium, a part of the small intestine close to the colon, although it can affect any tissue along the digestive tract. Patients with Crohn's disease commonly suffer from digestive disruptions, such as diarrhea. The disease appears to have a genetic basis with several genes implicated in the development of the disease.
Tumor Necrosis Factor
Tumor necrosis factor, or TNF, is a gene involved in Crohn's disease. TNF is secreted by cells within the body and circulates within tissue, or in the blood. Circulating TNF binds to receptors on the surface of target cells and triggers a signal within the cell. These signals get disrupted in Crohn's disease, which helps drive the progression of the disorder.
Variations within the TNF gene can affect TNF activity, and certain forms of the TNF gene are linked to Crohn's disease. A study published in "Diseases of the Colon and Rectum" in 1999 reported that one variation of the TNF gene was present in around 25 percent of Crohn's disease patients, especially those who were unresponsive to conventional treatment. Using TNF as a genetic marker for Crohn's disease may allow doctors to predict the patient's response to medication.
NOD2
NOD2, a signaling protein within the cell, also may serve as a genetic marker for Crohn's disease. Normal NOD2 regulates a protein called NF-kB, which helps regulate the body's immune response. In Crohn's disease, the immune response of the body is dysregulated, which helps drive the disorder.
A study published in "Nature" in 2001 found that a specific mutation to the NOD2 gene serves as a genetic marker for susceptibility to Crohn's disease. A mutation to NOD2, which generates a truncated and inactive form of the NOD2 protein, was associated with Crohn's disease, and this mutant form of NOD2 was unable to regulate NF-kB.
DLG5
DLG5 belongs to a large family of proteins called scaffold proteins, and is another gene that may act as a genetic marker for Crohn's disease. Scaffold proteins have no enzymatic function, but instead function to bring other proteins together to regulate signaling within cells. Mutated scaffold proteins cannot properly regulate signaling, which leads to disease. Variations to the DLG5 gene may regulate its activity within cells.
Variations to DLG5 have been linked to Crohn's disease in female patients. A study published in the "American Journal of Gastroenterology" in 2007 found that mutant form of DLG5, called DLG5 R30Q, was strongly associated with decreased development of Crohn's disease in female children. Therefore, DLG5 may act as a genetic marker to assess a female child's risk for developing Crohn's disease, and female patients carrying DLG5 R30Q may be protected from the disease.
References
- National Institutes of Heath: Crohn's disease-associated genetic marker is seen in medically unresponsive ulcerative colitis patients and may be associated with pouch-specific complications.
- National Institutes of Health: A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease.
- National Institutes of Health: DLG5 R30Q variant is a female-specific protective factor in pediatric onset Crohn's disease.
