A new US study suggests that the progress of age-related macular degeneration, a condition that leads to gradual loss of sight in the elderly, is influenced by common variations in two genes and lifestyle factors.

The study, which is reported in the Journal of the American Medical Association was led by Dr Johanna M Seddon, of Tufts-New England Medical Center and professor of ophthalmology at Tufts University in Boston, Massachusetts.

Dr Seddon and her colleagues found that common variants of two genes already linked to age-related macular degeneration (AMD), CFH and and LOC387115, increased the risk of progression of advanced AMD.

Possession of both risk genotypes, together with smoking and high body mass index increased the risk of progression by 19 times, the researchers found.

Macular degeneration is mostly a condition of old age, where the central part of the retina gets thinner or gradually deteriorates, sometimes with bleeding. The condition leads to loss of central vision, and the patient loses the ability to distinguish detail, such as reading print or recognizing faces.

Previous research has suggested that age-related macular degeneration (AMD) is linked to variations in two genes: CFH and LOC387715. This study aimed to find out to what extent these variants are linked with progression of AMD associated loss of vision.

The type of gene variation involved is something called Single Nucleotide Polymorphism (SNP, pronounced “snip”).

A SNP is a very small change in the sequence of a person’s DNA. 99 per cent of human DNA (the human genome) does not vary between individuals.

But one per cent does. And most of this variation comes from SNPs. An example of variation due to SNP might be in a small segment of DNA that is coded as AAGGTTA in one person and ATGGTTA in another person.

Such a small change can be harmless and have no effect, or it can mean the difference between being susceptible to a disease or not. Where SNPs have an effect, this is usually expressed in changes in the biological behaviour of the proteins coded by the affected segments of DNA.

The researchers used data from 1,466 white participants enrolled in the US Age-Related Eye Disease Study (AREDS). The participants were recruited from several centres across the US. Data was taken between 1990 to 2001 and the mean follow-up was 6.3 years.

281 participants were newly diagnosed with advanced AMD (consisting of “geographic atrophy, exudative disease, or AMD causing visual loss”) in one or both eyes during the duration of the study.

Analysis of genotypes to look for SNP variants was done in 2006.

The results showed that:

— Two particular gene variants (CFH Y402H and LOC387115 A69S polymorphisms) were each independently related to AMD progression.
— The progression was from early or intermediate stages to advanced stages of AMD.
— This was independent of demographic, smoking status, body mass index, and other factors.
— The size of the influence was 2.6 times for CFH (variant Y402H) and 4.1 times for LOC387115 (variant A69S).
— These odds ratios were for cases where two copies of the variant were present (one from each parent).
— Each gene variant affected the progress of AMD symptoms in slightly different ways.
— The presence of all adverse risk factors: both risk genotypes, smoking and being overweight (BMI 25 and over) increased the AMD progression risk 19-fold.

Dr Seddon and her team concluded that:

“Common polymorphisms in the genes CFH and LOC387715 are independently related to AMD progression after adjustment for other known AMD risk factors.”

They also said that the presence of these gene variants plus other factors such as smoking, having a BMI of 25 and over, “identify patients who are highly susceptible to developing advanced stages of this visually disabling disease”.

According to the Eye Digest (online resource written by University of Illinois Eye and Ear Infirmary Physicians), more than 1.6 million Americans have AMD. This compares with 4 million living with glaucoma and over 20 million over 65s with cataracts.

The number of Americans with an age-related eye disease is estimated to double over the next 30 years.

“Association of CFH Y402H and LOC387715 A69S With Progression of Age-Related Macular Degeneration.”
Johanna M. Seddon; Peter J. Francis; Sarah George; Dennis W. Schultz; Bernard Rosner; Michael L. Klein.
JAMA. 2007;297:1793-1800.
Vol. 297 No. 16, April 25, 2007

Click here for Abstract.

Click here for more information on What Are SNPs and How Are They Found? (US, National Center for Biotechnology Information).

Click here for more information on AMD (Eye Digest).

Written by: Catharine Paddock
Writer: Medical News Today