Rheumatoid arthritis (Rheumatoid arthritis) - HLA-DRB1 Genes, SLC22A4, PTPN22 (PTPN8), CIITA (MHC2TA), IRF5 and NFKBIL1.
Rheumatoid arthritis is a chronic disease that causes abnormal swelling, which mainly affects joints. Signs and symptoms include frequent pain, swelling and stiffness of the joints. Most often, the disease affects the small joints of the hands and feet, although larger joints such as the shoulders, hips and knees, may also be affected later. In addition, rheumatoid arthritis can also cause inflammation of other tissues and organs, including the eyes, lungs and blood vessels. Other signs and symptoms of the disease can include loss of energy, low fever, weight loss and anemia. Some affected individuals develop rheumatoid nodules that may develop under the skin and other body parts.
In general, the signs and symptoms of rheumatoid arthritis appear in mid to late adulthood. Many people will have episodes of symptoms followed by periods without symptoms for the rest of your life. In severe cases, affected individuals have persistent health problems for many years, related to the disease. Abnormal ignition can cause serious damage to the joints, which limits movement and can lead to significant disability.
Rheumatoid arthritis is probably the result of a combination of genetic and environmental factors, many of which are unknown. This disease is considered an autoimmune disorder, one of a large group of disorders that occur when the immune system attacks self tissues and organs of the body. In people with rheumatoid arthritis, the immune system causes abnormal inflammation in the synovium. When the synovium becomes inflamed, causing pain, swelling and stiffness of the joint. In severe cases, inflammation also affects the bone, cartilage and other tissues within the joint, causing more serious damage. Variations in several genes have been studied as risk factors for rheumatoid arthritis. Most of these genes are known to be involved in immune system function. The factor most significant genetic risk for rheumatoid arthritis are variations in the human leukocyte antigen (HLA), especially in the HLA-DRB1 gene. The proteins encoded by the HLA genes help the immune system to distinguish self proteins of body proteins produced by foreign invaders (such as viruses and bacteria). Changes in other genes, such as SLC22A4, PTPN22 (PTPN8), CIITA (MHC2TA), IRF5 and NFKBIL1 genes seem to have less impact on the risk of developing the disease.
It is believed that non - genetic factors play a role in rheumatoid arthritis. Although the mechanism is unclear, these factors can trigger the disease in people who are at risk. Some potential triggers include changes in sexual hormones (especially in women), occupational exposure to certain types of powder or fibers, and viral or bacterial infections. In the long term, smoking is a risk factor for developing rheumatoid arthritis and is also associated with signs and symptoms more severe in people who have the disease.
The HLA-DRB1 gene, located on the short arm of chromosome 6 (6p21.3), encodes a protein that plays a critical role in the immune system. This gene is part of a complex human leukocyte antigen (HLA) gene family called. This complex helps the immune system to distinguish self proteins body protein by foreign particles such as viruses and bacteria invading. Have identified several common variations of HLA-DRB1 gene are associated with the risk of developing rheumatoid arthritis. Variations of this gene are known genetic risk factor for the disease more significant. These variations affect the amino acids of the beta chain, introducing changes near the binding groove antigen recognition. This binding triggers the immune response that attacks foreign invaders. It is believed that the mechanism by which variations in the HLA-DRB1 gene increase the risk of rheumatoid arthritis associated with changes in binding of peptides that stimulate an abnormal immune response. However, many other genetic and environmental factors also contribute to a person 's overall risk of developing the disease. A few variations of HLA-DRB1 gene appear to decrease the risk of developing the disease. It is not clear why these particular changes may be protective.
The SLC22A4 gene, located on the long arm of chromosome 5 (5q31.1), encoding a protein organic cation transporter integral part of the plasma membrane containing transmembrane domains, and a nucleotide binding point. This protein transport is at least partially dependent on ATP.
The PTPN22 gene, located on the short arm of chromosome 1 (1p13.2), encodes a protein belonging to the PTP (protein tyrosine phosphatase) family. PTP proteins play a role in regulating signal transduction. These signals instruct the cell to grow and divide or to mature and take on specialized functions. The PTPN22 protein is involved in signaling that helps control the activity of T cells of the immune system. PTPN22 gene variation associated with autoimmune disorders changes the amino acid arginine with tryptophan amino acid at position 620 in the sequence of the PTPN22 (Arg620Trp or R620W) protein. This variation probably affects the activity of the protein, making it more difficult for the body control inflammation and prevent the immune system attacks its own tissues.
The CIITA gene, located on the short arm of chromosome 16 (16p13), encoding an acidic protein with a domain of transcriptional activation 4 LRRs and GTP binding domain. The protein is found in the nucleus and acts as a positive regulator of class II histocompatibility main complex gene transcription, and referred to as the "control factor" for the expression of these genes. The protein also binds GTP and the binding of GTP used to facilitate their own transport in the nucleus. Once in the nucleus, it does not bind DNA but uses an intrinsic activity acetyltransferase (AT) to act in a similar way coactivator.
IRF5 gene, located on the long arm of chromosome 7 (7q32), encodes a protein called interferon regulatory factor 5 (IRF5), which acts as a transcription factor. The protein binds to specific DNA regions that regulate the activity of genes that produce interferon and other cytokines. There is some evidence that certain variations IRF5 gene are associated with an increase in gene activity and high cytokine. However, it is unknown what role, if any, they play these effects in increasing the risk of rheumatoid arthritis. It is believed that a combination of genetic and environmental factors may contribute to the development of this disease.
The NFKBIL1 gene, located on the short arm of chromosome 6 (6p21.3), encodes a divergent member of the family of proteins I-kappa-B. This protein is involved in regulating the immune response.
The inheritance pattern of rheumatoid arthritis is uncertain because many genetic and environmental factors appear to be involved. However, having a close relative with rheumatoid arthritis probably increases the risk of developing the disease.
Tests in IVAMI: in IVAMI perform the detection of mutations associated with rheumatoid arthritis, by complete PCR amplification of the exons of the HLA-DRB1, SLC22A4, PTPN22 (PTPN8), CIITA (MHC2TA), IRF5 and NFKBIL1 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).