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Common genetic variants associated with advanced forms of age-related macular degeneration
Written by NetDoc.com Medical News Feed   

Variations of two common genes are associated with progression to more advanced forms of age-related macular degeneration, and factors such as smoking and being overweight greatly increase this risk, according to a study in the April 25 issue of JAMA.

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Age-related macular degeneration (AMD; when the center of the inner lining of the eye suffers thinning, atrophy, and in some cases bleeding), which can lead to visual impairment and legal blindness, is associated with variations in the genes CFH and LOC387715. It is believed that no previous studies have examined the relationships between common variations in these genes and progression from early or intermediate stages of maculopathy (disease in a part of the retina) to advanced forms of AMD associated with visual loss, according to background information in the article.

Johanna M. Seddon, M.D., Sc.M., of Tufts-New England Medical Center, Boston, and colleagues assessed whether certain genetic variants have prognostic importance for progression to advanced AMD and related visual loss. The study included 1,466 white participants in the Age-Related Eye Disease Study (AREDS), a U.S. multicenter clinical trial conducted from 1990 to 2001 with an average follow-up time of 6.3 years. During the study, 281 participants progressed to advanced AMD in one or both eyes, which included: geographic atrophy (results in thinning and discoloration of the retina), exudative disease (the escape of fluid, cells, and cellular debris from blood vessels), or AMD causing visual loss. Genotypic analysis was conducted in 2006.

The researchers found that the genetic polymorphisms, CFH Y402H and LOC387715 A69S, were associated with progression to more advanced AMD, with the risk of progression being 2.6 times higher for CFH and 4.1 times higher for LOC387715 risk genotypes after controlling for other factors associated with AMD. The probability of progression was 48 percent for the highest-risk genotype vs. 5 percent for the low-risk genotypes. The presence of all adverse factors (both risk genotypes, smoking, and body mass index 25 or greater) increased risk 19-fold. Smoking and high body mass index increased odds of progression within each risk genotype.

"...individuals with the risk genotype, if identified and appropriately advised, may be more motivated to adhere to healthy lifestyle habits, which are known to be related to a reduced risk of AMD. These include not smoking, maintaining a normal or lean weight, getting exercise, and eating an antioxidant-rich diet with fruits and vegetables as well as fish," the authors write.

"We believe it is premature at this time to consider genotyping individuals with various stages of AMD. Screening should consider (1) that genotyping of about 30 individuals with drusen/pigment changes would be required to identify one individual who is homozygous for the risk allele for both genes and (2) the observation that many but not all individuals with those genotypes will develop the disease. However, in the future, a risk profile that includes genetic and environmental factors, such as the one calculated herein, may ultimately lead to targeted screening and closer monitoring of individuals who are at higher risk of visual loss due to AMD progression."
(JAMA. 2007;297:1793-1800)

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