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HEALTH NEWS

Scientists ID Genes Linked to Age-Related Blindness

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 07 March, 2006  15:27 GMT

macular degeneration genes
'I am not aware of any other complex disorder where nearly 75 percent of genetic causality has been identified,' said Professor Rando Allikmets of Columbia University in New York, who led the research.
Scientists in the United States have discovered that 74 percent of patients with age-related macular degeneration (AMD), which affects one in 10 people aged over 60, have mutations in one or both key genes.

The findings suggest new targets for drugs that might slow or even prevent the progressive damage to the retina that occurs in AMD, which has irreversibly blinded an estimated 50 million people worldwide and which currently affects 500,000 people in the United Kingdom.

The study is also the first to identify the genes that explain so many cases of a complex disorder in which more than one gene is involved.

75% of Genetic Causation Identified

Many single-gene disorders that are caused by one mutation, such as Huntington's disease or cystic fibrosis, are well understood. But scientists have struggled to pin down the triggers of other conditions in which more than one mutation is involved.

"I am not aware of any other complex disorder where nearly 75 percent of genetic causality has been identified," said Professor Rando Allikmets of Columbia University in New York, who led the research.

Macular degeneration causes the gradual loss of sight owing to damage to the macula, a particularly sensitive portion in the center of the retina that is responsible for fine and detailed vision.

While central vision is first to go, the disease can eventually cause total blindness.

Long Been Known to Run in Families

Although the condition has long been known to run in families and to have a strong genetic component, recent research has linked several variants of a gene known as Factor H to an increased risk of developing AMD.

Factor H produces a protein that helps to shut down the immune response to bacterial or viral infections once the invading pathogens have been eliminated, preventing damage to healthy tissue. The mutated versions appear to cause extended inflammation that can harm the retina.

The Factor H gene alone, however, can explain only between 30 and 60 percent of AMD cases, and its action has puzzled researchers as a third of people with an apparently harmful mutation do not develop the disease. This led the Columbia team, which identified the role of Factor H, to seek other genes that might play a part.

A new genetic analysis of 1,300 people has now shown that a second gene, known as Factor B, also has a significant effect on AMD. It is the mirror image of Factor H, starting rather than stopping the immune response, and certain variants appear to protect the eye when a person has a harmful Factor H mutation.

The research, which was published yesterday in the journal Nature Genetics, suggests that between them, Factor H and Factor B account for 74 percent of AMD cases.




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