Ankylosing spondylitis (ankylosing spondylitis) - Genes ERAP1, HLA-B, IL1A, and IL23R.  

Ankylosing spondylitis is a form of chronic inflammatory arthritis primarily affecting spine. This disease is characterized by back pain and stiffness that usually appears in adolescence or early adulthood. Eventually, the rearward movement gradually limited, since the vertebrae fuse. This progressive bone fusion is called ankylosis.

Early symptoms of ankylosing spondylitis are due to inflammation of the iliac crest and sacrum. Inflammation gradually spreads to the joints between the vertebrae, called spondylitis. Ankylosing spondylitis may involve other joints such as the shoulders, hips, and, less frequently, knees. As the disease progresses, it can affect the joints between the spine and ribs, restricting the movement of the chest and makes it difficult to breathe deeply. People with advanced disease are more prone to fractures of the vertebrae. In addition, up to 40% of cases, the disease affects the eyes leading to acute iritis, which causes eye pain and photophobia. In rare cases, the disease can also lead to serious complications involving the heart, lungs and nervous system.

Ankylosing spondylitis is probably due to a combination of genetic and environmental factors, most of which have not been identified. However, we have identified variations in ERAP1, HLA-B, IL1A and IL23R genes influence the risk of developing this disease.

The ERAP1 gene, located on the long arm of chromosome 5 (5q15), encodes a protein called endoplasmic reticulum aminopeptidase 1. As the name suggests, this protein is active in the endoplasmic reticulum, involved in the processing and transport of proteins. This protein is an aminopeptidase, which cleaves other proteins into peptides. The protein encoded by this gene has two main functions, both important for normal immune system function. First, cleaves cytokine receptors on the cell surface. Cleaving these receptors reduces their ability to transmit chemical signals in the cell, which affects the process of inflammation. Second, cleaves many types of proteins into small peptides that can be recognized by the immune system. These peptides are exported to the cell surface, where they bind to major histocompatibility complex proteins class I (MHC). If the immune system recognizes as foreign peptides, as occurs with viral or bacterial peptides, it responds by activating the infected cell to self - destruct. Several polymorphisms have been identified in the gene ERAP1 influence the risk of ankylosing spondylitis. Each of these variations in a single amino acid change aminopeptidase 1 endoplasmic reticulum. Although little is known about the effects of these variations, it is likely that changes in protein structure alter any of its two main functions.

The HLA-B gene, located on the short arm of chromosome 6 (6p21.3), encodes a protein that plays an important role in the immune system. HLA-B is part of a family of genes called human leukocyte antigen complex (HLA). The HLA complex helps the immune system to distinguish self proteins of the organism, of the proteins produced by the invaders as viruses and bacteria. Each HLA gene has different normal variations, allowing the immune system reacts to each individual a wide range of foreign proteins. A particular variation of the HLA-B gene called HLA-B27 increases the risk of ankylosing spondylitis. Although it is unclear how the HLA-B27 variation increases the risk, it is likely that either can induce peptides trigger an immune reaction which results in the inflammatory process that causes arthritis or the characteristic inflammation is due to misfolding of HLA-B27 protein or the presence of abnormal forms of the protein on the cell surface. Although many people with ankylosing spondylitis have the HLA-B27 variation, most people with this version of the HLA-B gene never develop the disease.

The IL1A gene, located on the long arm of chromosome 2 (2q14), encoding interleukin-1 alpha protein. Interleukins are a group of proteins that are involved in cell to cell communication and have a wide variety of functions within the immune system. Interleukin-1 alpha is described as "proinflammatory" because it stimulates the activity of genes involved in inflammation and immunity. This protein plays a key role in protecting the body from foreign invaders such as bacteria and viruses. It is also involved in bone resorption, decomposition and removal of bone tissue that is no longer needed. They have identified several polymorphisms in the IL1A gene that influence the risk of ankylosing spondylitis. Each of these variations in a single amino acid changes interleukin-1 alpha. Although not clear how these changes alter the function of the protein, it is likely that the effects of IL1A variations are related to the role of interleukin-1 alpha in promoting inflammation.

The IL23R gene, 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. Several polymorphisms in the gene IL23R influence the risk of ankylosing spondylitis. One such variation appears to reduce the likelihood of developing the disease. This genetic change replaces the amino acid arginine to the amino acid glutamine at position 381 of the protein (Arg381Gln). However, other variations IL23R appear to increase the risk of developing ankylosing spondylitis. Although it is unclear how these changes are related to the risk of developing the disease, it is likely that the effects of the IL23R variations are related to the role of interleukin 23 receptor in inflammation.

Although ankylosing spondylitis can occur in more than one person in a family, is not a purely genetic disease. Multiple genetic and environmental factors likely play a role in determining the risk of developing this disease. As a result, inheriting a genetic variation linked to ankylosing spondylitis does not mean a person will develop the disease, even in families where more than one member has altered. For example, about 80% of children who inherit HLA-B27 a parent with ankylosing spondylitis not express the disease.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with ankylosing spondylitis, by complete PCR amplification of the exons of ERAP1, HLA-B, IL1A and IL23R 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).