Model predicts advanced AMD development

June 18, 2008

A new model can predict the percentage of people who will develop advanced age-related macular degeneration (AMD) at various ages. The model, which is based on well-established risk factors for the disease such as age, smoking, and genetics, considers high-risk, intermediate-risk, and low-risk genotypes. Genotypes are more predictive of the risk of developing advanced AMD than is age.

A new model based on well-established risk factors for age-related macular degeneration (AMD) can predict the percentage of people who will develop advanced AMD at various ages. The model considers high-risk, intermediate-risk, and low-risk genotypes. Investigators found that the genotypes of only two AMD genes are more predictive of the risk of developing advanced AMD than age.

 "There have been numerous epidemiologic and genetic studies of AMD that have pointed out the risk factors for AMD – three of which are generally accepted by all groups, namely, age, smoking, and genetics. The last is recently the most newsworthy," said Thaddeus Dryja, MD. He is clinical professor of ophthalmology, Harvard Medical School, Boston, and head of translational medicine in ophthalmology at Novartis.

Seven genes thus far have been associated with AMD. Dr. Dryja demonstrated that the risk ratios of the genotypes vary from about 1.6 for the ERCC6 gene to about 11 for the HTRA1 LOC complex, with 1 being the arbitrary reference genotype. In a clinical setting, however, can this information be translated into the actual risk factor for AMD among individual patients? Dr. Dryja asked rhetorically.

To answer this question, he, Sergej Aksenov, PhD, and colleagues at the Novartis Institutes for BioMedical Research in Cambridge, MA, translated data in the literature into the precise risks for AMD based on an individual's age, smoking status, and two of the primary AMD genes, namely, the complement factor H gene and HTRA1 LOC 387715 gene.

During this process, Dr. Dryja and colleagues surveyed 15 studies of Caucasian patients for whom there were genotypic data on the two loci. The investigators also looked up the prevalence of AMD by age and sex, the prevalence of smoking by age and sex, the relative risk of AMD in individuals who smoke compared with those who do not smoke, and the demographics of the population.

"There were assumptions that we had to make, but I believe that those assumptions were reasonable. The main assumptions were that an individual's genotype at the AMD loci does not influence whether the individual will smoke and that there is no difference in longevity depending on genotype at AMD genes," he said.