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

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).

Previous studies found that AMD is associated with variations in the genes CFH and LOC387715. In this study, genotypic analysis showed that the genetic polymorphisms CFH Y402H and LOC387715 A69S were associated with progression to advanced AMD. The risk of progression is 2.6 times higher for CFH and 4.1 times greater for LOC387715 risk genotypes after controlling for other factors associated with AMD. The researchers found that the probability of progression is 48% for the highest-risk genotype vs. 5% for the low-risk genotypes.

The presence of all adverse factorsboth risk genotypes, smoking, and body mass index (BMI) of 25 or greaterincreased the risk of progression to advanced AMD 19-fold. Smoking and high BMI also 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, the authors write. 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 say that it is premature to consider genotyping individuals various stages of AMD. 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, they say.


Seddon JM, Francis PJ, George S, et al. Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration. JAMA 2007 Apr 25;297(16):1793-800.

Vol. No: 144:05Issue: 5/15/2007