Ulcerative colitis (ulcerative colitis) - Genes ABCB1, IL10RA, IL10RB, IL23R, IRF5 or PTPN2


Ulcerative colitis, also known as inflammatory bowel disease type or idiopathic proctocolitis ulcerative colitis is a chronic disease affecting the digestive tract, characterized by abnormal swelling of the inner surface of the rectum and colon. Inflammation usually leads to development of ulcers in the large intestine. Ulcerative colitis usually appears between 15 and 30 years, but may do so at other ages. Inflammation tends to occur several times throughout life, which makes the signs and symptoms are recurrent.

The most common symptoms of ulcerative colitis include abdominal pain and cramping, and frequent diarrhea, which usually blood, pus or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, fatigue and fever. Chronic bleeding and ulcerated inflamed intestinal tissue can cause anemia in some affected individuals. People with this condition have difficulty absorbing fluids and dietary nutrients and often have weight loss. Children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys or liver, probably due to abnormal inflammation. A rare complication of ulcerative colitis is toxic megacolon, which can be potentially fatal. Toxic megacolon involves a widening of the colon and sepsis. Ulcerative colitis also increases the risk of developing colon cancer, especially in those in which the colon is inflamed in its entirety and people who have had ulcerative colitis for 8 or more years.

Ulcerative colitis is a common form of inflammatory bowel disease (IBD). Another type of IBD disease called Crohn's disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn's disease may cause inflammation in any part of the digestive system, and inflammation extends deep into the intestinal tissue.

Ulcerative colitis is probably due to a variety of genetic and environmental factors. Some studies have identified dozens of variations of genes may be linked to ulcerative colitis; however, the role of these variations are not fully understood. It is speculated that this disease may be due to changes in barrier function of the intestinal mucosa or abnormal immune response to bacteria in the digestive tract, which may be influenced by genetic variations. Several of the genes may be associated with ulcerative colitis are involved in the protective function of the intestines. The inner surface of the intestines provides a barrier that protects the body's tissues of bacteria living in the intestines and toxins that pass through the digestive tract. It is believed that a break this barrier allows contact between intestinal tissue and bacteria and toxins, which can trigger an immune reaction. This immune response can lead to chronic inflammation and digestive problems characteristic of ulcerative colitis.

Other disease - associated genes are involved in the immune system, in particular in the maturation and function of T cells T cells identify foreign substances and defend the body against infection. Genetic variations may cause some individuals more prone to an overactive immune response against bacteria and other microbes in the gut, which can cause chronic inflammation that occurs in ulcerative colitis. Another possible explanation is that ulcerative colitis occurs when the malfunction of the immune system attacks the intestinal cells, causing inflammation.

The ABCB1 gene (ATP binding cassette subfamily B member 1), located on the long arm of chromosome 7 (7q21.12), encodes a protein member of the MDR / TAP subfamily. Members MDR / TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is a dependent efflux pump ATP drug for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug resistant cells and medium frequency with the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier.

The gene IL10RA (Interleukin 10 receptor alpha subunit), located on the long arm of chromosome 11 (11q23), encoding a protein receptor for interleukin 10. This protein is structurally related to interferon receptors. It has been shown to mediate the immunosuppressive signal of interleukin 10 and therefore inhibits the synthesis of proinflammatory cytokines. This receptor promotes survival of myeloid progenitor cells through the insulin receptor pathway substrate-2 / PI 3-kinase pathway / AKT. Activation of this receptor leads to phosphorylation of tyrosine kinases TYK2 and JAK1.

The gene IL10RB (Interleukin 10 receptor beta subunit), located on the long arm of chromosome 21 (21q22.11), encoding a protein of the family of cytokine receptors. It has been shown that coexpression of this protein is required and IL10RA for signal transduction induced by IL10. Dimer IFNLR1 / IL10RB is a receptor for the cytokine ligands and IFNL3 IFNL2 half its antiviral activity. The ligand / receptor complex stimulates activation of the signaling pathway JAK / STAT causing expression of IFN stimulated (ISG), which contribute to the antiviral state genes.

The IL23R gene (Interleukin 23 receptor), located on the short arm of chromosome 1 (1p31.3), encoding the protein receptor for interleukin 23. This protein is embedded in the cell membrane of various types of immune system cells, including T cells, natural killer (NK) cells, monocytes and dendritic cells. These cells identify foreign substances and defend the body against infection and disease. Cell surface receptor, interleukin 23 interacts with a protein called interleukin 23. When interleukin 23 protein binds to its receptor, a series of chemical signals within the cell are fired. These signals promote inflammation and help coordinate the immune system 's response to foreign invaders such as bacteria and viruses.

The gene IRF5 (Interferon regulatory factor 5), located on the long arm of chromosome 7 (7q32), encoding a regulatory protein called interferon factor 5 (IRF5), which acts as a transcription factor. When a virus is detected in a cell, the gene encodes IRF5 IRF5 protein. The protein binds to specific DNA regions that regulate the activity of genes encoding interferons and other cytokines. Cytokines are proteins that help fight infection and inflammation by regulating the activity of immune system cells. In particular, interferons control the activity of genes that help block virus replication, and stimulate the activity of certain immune system cells known as natural killer cells (NK cells).

The PTPN2 (protein tyrosine phosphatase, non-receptor type 2), located on the short arm of chromosome 18 (18p11.3-p11.2), encodes a protein family member protein tyrosine phosphatase (PTP). Members of the PTP family share a highly conserved catalytic motif that is essential for catalytic activity. PTPs are known to be molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and transforming oncogene signaling.

The inheritance pattern of ulcerative colitis is unknown because that may be involved many genetic and environmental factors. Although the inheritance pattern of this disease is unclear, having a relative with ulcerative colitis increases the risk of developing the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with ulcerative colitis, by complete PCR amplification of the exons of ABCB1, IL10RA, IL10RB, IL23R, IRF5 PTPN2 or genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).