By combining the tools of high-throughput biology and statistical genetics, scientists at Rockefeller University, Yale University School of Public Health and the National Eye Institute have identified a gene that confers susceptibility to age-related macular degeneration (AMD), the most common cause of vision loss in the United Sates for those over 60. Reported in the March 10 issue of Science Express, the finding opens the door for new investigations of the role of genes in developing AMD and possible treatments for this disease. “We have shown that a variant, or polymorphism, of the complement factor H gene, which alters a protein whose normal function is to regulate the immune system’s attack of foreign invaders and abnormal cells, is involved in the development of AMD,” says senior co-author Jürg Ott, Ph.D., professor and head of the Laboratory of Statistical Genetics at Rockefeller. “We believe this polymorphism is a strong risk factor for the disease.” The gene variant, known as a single nucleotide polymorphism (SNP), derives from a single letter difference in the genetic sequence of DNA. Some of these differences may change a gene’s protein products in ways that may confer susceptibility to -- or protection from -- diseases. In this case, the complement factor H (CFH) SNP associated with AMD encodes for a different amino acid, as histidine substitutes for tyrosine at a specific position. The CFH gene lies in a region of human chromosome 1 that had been linked previously to AMD through family studies by other researchers. The research team was led by senior co-author Josephine Hoh, Ph.D., an assistant professor in the Division of Chronic Disease Epidemiology at Yale’s School of Public Health. Before joining Yale in 2003, Hoh was a research assistant professor in Ott’s lab. For the research reported in Science Express, Hoh used DNA taken from blood samples collected for the National Eye Institute-sponsored Age-Related Eye Disease Study (AREDS). The AREDS was designed to learn more about the natural history and risk factors of AMD and cataract and evaluate the effect of high doses of antioxidants and zinc on the progression of these conditions.
