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Variation in Three Genes Influences Risk of Age-Related Macular Degeneration

Published: Thursday, September 07, 2006
Last Updated: Thursday, September 14, 2006
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Researchers discover a common, noncoding variant in the CFH gene that is associated with AMD.

Researchers in Boston have discovered a common, noncoding variant in the Complement Factor H (CFH) gene that is associated with age-related macular degeneration (AMD).

Their analyses combine this variant with all previously reported variants to estimate individual risk of advanced AMD.

They observed additive accumulation of risk from alleles at these three genes, including CFH on chromosome 1, complement factor B (BF) and complement component 2 (C2) genes on chromosome 6, and the LOC gene on chromosome 10.

They estimate that genotypes related to five variants in these three genes explain about half the sibling risk of AMD in the study population. Results are published online in Nature Genetics

They studied 2,172 unrelated European-descended individuals 60 years of age or older, who were diagnosed on the basis of ocular examination and ocular photography (1,238 affected individuals and 934 controls).

Affected individuals were defined as those having advanced AMD related to visual loss with either geographic atrophy (dry) or neovascular (wet) disease.

Controls were individuals without AMD. The mean age was 74 for controls (54% female) and 78 years for affected individuals (55% female).

Both Illumina and Sequenom methods were used to genotype about 1540 single nucleotide polymorphisms.

"The overall implication of this study is that depending on your genotype related to these five variants in three genes, and most likely more to be discovered, preventive and therapeutic drug targets may be better designed and tailored to an individual's need, ie., personalized medicine," said Johanna M. Seddon, M.D., Director of the Epidemiology Unit and Macular Degeneration specialist at the Massachusetts Eye and Ear Infirmary, and Associate Professor at Harvard Medical School.

This study evaluated a large number of samples from individuals with advanced AMD, including both geographic atrophy or "dry" AMD, and neovascular disease or "wet" AMD, which cause visual loss.

It is noteworthy that no differences were found between these subtypes of advanced AMD with respect to the variations found in the genes.

Dr. Seddon and her colleagues previously reported that the heritability of AMD is high (46% to 71%) in a large US cohort of elderly twins (Arch Ophthalmol 2005), and that another common CFH variant as well as smoking and higher body mass index are independently related to advanced AMD (Human Heredity 2006).

A decade ago they reported the increased risk of AMD attributable to cigarette smoking (JAMA 1996).

They also found that high body mass index is a risk factor for progression of the disease. (Arch Ophthalmol 2003).


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