This article is more than 5 years old. Information may no longer be current.
Researchers link common genetic variants with progression to advanced AMD
Click Here to Manage Email Alerts
Variations in two common genes are associated with progression to advanced forms of age-related macular degeneration, and the presence of risk factors such as smoking and obesity significantly increases that risk, a prospective study found.
Johanna M. Seddon, MD, ScM, of Tufts-New England Medical Center, Boston, and colleagues investigated whether variations in the genes CFH and LOC387715 could have "prognostic importance" for progression to advanced AMD. The researchers reviewed data for 1,466 white participants in the Age-Related Eye Disease Study (AREDS) followed for an average of 6.3 years. Of these participants, 281 progressed to advanced AMD in one or both eyes, which included geographic atrophy, exudative disease or vision loss, according to a press release from the Journal of the American Medical Association announcing the study findings.
From genotypic analyses conducted in 2006, Dr. Seddon and colleagues found that two genetic polymorphisms — CFH Y402H and LOC387715 A69S — were associated with progression to advanced AMD.
In particular, patients with a polymorphism in CFH had a 2.6-times higher risk of progression, while those with a polymorphism in LOC387715 had a 4.1-times higher risk after controlling for other factors. The probability of progression was 48% for the highest-risk genotype vs. 5% for the low-risk genotypes, according to the release.
In addition, the presence of all adverse factors, including both risk genotypes, smoking and a body mass index (BMI) of 25 or greater, increased the risk of progression 19-fold. Smoking and a higher BMI also increased the risk of progression within each risk genotype, the release said.
However, the authors do not suggest beginning to genotypically screen 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," they wrote.
"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," they said.
The study is published in the April 25 issue of Journal of the American Medical Association.