Related macular degeneration with age (Age-related macular degeneration) - Genes ARMS2, CFH and HTRA1  

Macular degeneration is age - related eye disease that is the leading cause of vision loss in the elderly in developed countries. Typically, vision loss is evident among the sixty or seventy years old and tends to worsen over time. Related macular degeneration with age primarily affects the central vision, which is required for detailed tasks such as reading, driving and recognizing faces. The vision loss in this disease, causes a gradual deterioration of retinal cells. Specifically, macular degeneration related to age affects the macula, which is responsible for central vision. Generally, peripheral vision and night vision are not affected.

They described two main types of related macular degeneration with age, known as the dry form and wet form. The dry form is more common, accounting for between 85% and 90% of all cases of the disease. It is characterized by an accumulation of yellow deposits under the retina, and a loss of the slow and progressive vision. Generally, this type affects vision in both eyes but often vision loss occurs before one eye than the other. For its part, the wet form is associated with severe vision loss can worsen quickly. This form is characterized by the growth of abnormal fragile under the macula blood vessels. These vessels leak blood and fluid, damaging the macula and causes central vision is blurred and distorted.

This process is due to a combination of genetic and environmental factors. Many of these factors have been identified, but some remain unknown. Environmental factors that can increase the risk of developing the disease include age, smoking, high blood pressure, heart disease, high fat diet or is low in certain nutrients (antioxidants and zinc), obesity, and exposure to ultraviolet (UV) radiation from sunlight. It is likely that changes in many genes constitute potential risk factors for the disease. Genes that contribute most to the risk of developing the disease are ARMS2 genes (age-related maculopathy susceptibility 2), CFH (complement factor H) and HTRA1 (HtrA serine peptidase 1). Other genes that are associated with macular degeneration include age - related genes involved in the transport and processing of high density lipoproteins and genes that have been associated with other forms of macular disease. These genes are ABCA4, APOE, ARMS2, ASPM, BEST1, C2, C3, C9, CETP, CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, COL8A1, COL10A1, CST3, CX3CR1, ELOVL4, ERCC6, F13B , FBLN5, FILIP1L, FRK, HMCN1, HTRA1, LIPC, MAP2, TIMP3, TNFRSF10A and VEGF.

The ARMS2 gene (age-related maculopathy susceptibility 2), located on the long arm of chromosome 10 (10q26.13), encoding a protein whose function is unknown. This protein is found primarily in the placenta and in the retina. However, it is unclear what role, if any, played by the protein in early development or normal vision. Several polymorphisms have been identified in and near the ARMS2 gene may explain the association with related macular degeneration with age. The best studied of these variations, rs10490924, alters a single amino acid in the protein ARMS2. Another common variation, a complex change that removes a segment of ARMS2 gene and insert the new genetic material, can also contribute to the risk of developing the disease; however, it is unclear how polymorphisms in the gene ARMS2 could be related to the disease. The ARMS2 gene is next HTRA1 gene. Changes in this gene have also been studied as a risk factor for the disease. Because the two genes are so close, it is difficult to say whether changes in a gene or possibly changes in both genes represent the greatest risk of disease. Related macular degeneration with age is a complex disease that probably is due to a combination of multiple genetic and environmental factors.

The CFH gene (complement factor H), located on the long arm of chromosome 1 (1q32) encodes protein helps regulate a part of the body 's immune response known as the complement system protein complement factor H. This. The complement system is a group of proteins that act together to destroy foreign invaders (as bacteria and viruses), trigger an inflammatory response, and remove waste from cells and tissues. This system must be carefully regulated to direct all the unwanted compounds and not attack the healthy cells of the organism. In this regard, the complement factor H and several related proteins protect healthy cells by preventing activation of the complement system when not needed. Several variants have been identified in and near the CFH gene in people with macular degeneration related to age. The Tyr402His polymorphism seems to be associated with an increased risk of developing the disease. People who carry one copy of this polymorphism have a 2.5 times greater risk of developing macular degeneration related to age compared to people without the polymorphism, whereas people who carry two copies of the polymorphism are six times more risk. However, most people with these variants never develop the disease.

The HTRA1 gene (HtrA serine peptidase 1), located on the long arm of chromosome 10 (10q26.3), encodes a protein found in many organs and tissues. This protein is a serine protease type, having an active center that cleaves other proteins into smaller units. The HTRA1 enzyme helps break down many other kinds of proteins in the extracellular matrix. The HTRA1 enzyme also binds to proteins in the growth factor family transformant beta (TGF-?) and inhibits its ability to transmit chemical signals. The TGF-? proteins normally help control many important cellular functions, including cell growth and proliferation, differentiation, motility and apoptosis. TGF-? also plays an important role in angiogenesis. Additional functions HTRA1 enzyme can include microtubule stabilization comprising the cytoskeleton, the mineralization of the bones, as well as a tumor suppressor function. Several polymorphisms have been identified in the HTRA1 gene may account for its association with related macular degeneration with age. One variant, rs11200638, is in the region that starts encoding the enzyme HTRA1; however, it is unclear how a polymorphism in the gene HTRA1 could be related to macular degeneration related to age.

Generally, macular degeneration related to age has no clear pattern of inheritance although in some cases appear to be inherited. It is estimated that between 15 and 20% of people with macular degeneration related to age have at least one first - degree relative , like a brother with the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with macular degeneration related to age, by complete PCR amplification of the exons of ARMS2, CFH and HTRA1, respectively, and subsequent sequencing genes.

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).