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Senior Citizen Health & Medicine
Blinding Age-Related Macular Degeneration Progress
Linked to Common Genetic Variants
Obesity and smoking found to greatly increase the risk
April 24, 2007 - 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 Journal of the American Medical Association.
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.
AMD is the leading cause of blindness in senior citizens.
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 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."
>>
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