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Gene Linked With Aggressive 'Wet' Form Of AMD

Two recent articles in Science by researchers at Yale School of Medicine has reported about a gene variant that increases the risk of developing //the aggressive 'wet' form of age-related macular degeneration (AMD), the most common cause of blindness in people over age 50.

AMD causes light-sensitive cells in the retina to break down, resulting in progressive loss of central vision. Of the two forms of AMD, the 'dry' is more common than the 'wet' form. Wet macular degeneration can rapidly lead to blindness, while the dry AMD progresses more slowly.

Last year, Josephine Hoh, associate professor in the Departments of Epidemiology & Public Health and Ophthalmology at Yale and senior author on one of the two new studies, identified a gene for dry AMD and found that both wet and dry AMD are associated with a variant in the complement factor H (CFH) gene on chromosome 1.

Hoh now reports they have found a single nucleotide polymorphism (SNP)—a one-base change in the sequence—of the regulatory part of the HTRA1 gene on chromosome 10 that leads to greatly increased risk of developing the wet form of AMD.

According to Hoh, buildup of abnormal blood vessels in Caucasian patients is compounded by development of large waste deposits called drusen. Chinese patients, she said, develop little to no drusen and progress directly to wet AMD. This study demonstrates that these two major genes, CFH and HTRA1, in two different biological pathways, each affect the risk for a distinct component of the AMD phenotype: CFH influences the drusen of dry AMD, whereas HTRA1 influences blood vessel development, the hallmark of the wet disease type. When the two processes are combined, it leads to the composite characteristics that are seen in some cases of AMD.

Hoh, her collaborators in Hong Kong, and her colleagues at Yale including Michael Snyder and Colin Barnstable in the Departments of Molecular, Cellular and Developmental Biology and Molecu
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