Investigators have identified a gene that is "strongly associated" with a person's risk for developing age-related macular degeneration (AMD). The finding was made by four independent teams, which include researchers with the National Eye Institute (NEI) and the National Cancer Institute, components of the National Institutes of Health (NIH), and other leading research centers.
The four studies described in the journal Science (April 15, 2005 issue) and PNAS used distinct but complementary methods to screen the genomes from non-overlapping groups of AMD patients. Yet all four studies came up with a commonly inherited variant of the same gene, called complement factor H (CFH).

Complement factor H (CFH) gene has been determined to be strongly associated with a person's risk for developing macular degeneration (AMD). A tyrosine-histidine change at amino acid 402 in complement factor H (CFH) on chromosome 1 results in the formation of a CFH gene variant. The sequence change is in a region of CFH that binds heparin and C-reactive protein. People whose genetic makeup includes this variant of the CFH gene are more likely to develop AMD. CFH gene variant may be responsible for about half of the 15 million cases of macular degeneration in the US. The odds of developing macular degeneration are increased by about 2.5 to 5.5 times if one has the CFH gene variant.
CFH gene is involved in regulating the inflammatory pathways (alternate complement pathway). This implies that inflammation too plays an important role in macular degeneration development. Blood levels of an inflammatory marker C-Reactive Protein (CRP) have also been found to be elevated in macular degeneration. (Science. 2005 Apr 15;308(5720):419-21, Science. 2005 Apr 15;308(5720):421-4, Science. 2005 Apr 15;308(5720):385-9)

The protein encoded by the CFH gene variant increases AMD risk by failing to bind to receptors on the cells of the retina and the choroid, which prevents it from inhibiting the inflammatory pathway. Unchecked, the pathway would cause inflammation in the retina and the surrounding blood vessels.
CFH prevents uncontrolled complement activation and inflammation; hence a mutation in CFH will increase inflammation and its consequences. By reducing the excessive complement (inflammatory pathway) activation that occurs in macular degeneration, we may be able to slow down the disease progress. Additionally, detecting the gene variant might one day be used in combination with imaging technologies to identify individuals at high risk of developing advanced AMD earlier than is currently possible. (JAMA. 2005 Apr 20;293(15):1841-5)

Discovery of the macular degeneration gene may lead to early detection and new strategies for prevention and treatment of macular degeneration and control of inflammation may become an additional goal in treating macular degeneration.

More about Complement System, CFH and Inflammation
The complement system is part of the innate defence mechanism consisting of over 30 serum proteins involved as a cascade that results in the rapid delivery of activated enzymes which create micropores within foreign objects such as microbes resulting in cellular lysis and inflammation (Eye May 2007). The CFH is part of the alternative pathway and it is specifically involved with the inhibition of the cascade in combination with other proteins. It is thought that for some reason in AMD patients, abnormal regulation of the complement cascade occurs at a local level within Bruch's membrane and adjacent retinal pigment epithelial cells resulting in uncontrolled compliment activation and consequent drusen formation.

Should genetic testing be recommended for macular degeneration patients?
Not at this time - according to an editorial in the journal Ophthalmology (Edwards AO. Ophthalmology 2006;113:509-10). The prevalence of one high risk drusen (size greater than 125 µm) is estimated at 4.3 million in the 30.5 million white persons 65 years or older in the United States. Given the prevalence of the CFH genetic variation (38%), an estimated 11.5 million white persons 65 or older would carry at least one CFH variant. Many more people would test positive for the CFH variant than have AMD. Also CFH variants probably do not predict the risk of developing complications of AMD. Thus, at this time the diagnosis and management of AMD remains based on clinical examination, not genetic testing.

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