For the study published in NEJM, the researchers recruited 402 people with AMD and 429 healthy subjects. They obtained blood samples from the study subjects, which they used to extract DNA that was then examined for variations in genes that code for proteins called fibulins. The researchers chose the fibulin genes because previous studies by Stone, Sheffield and their colleagues identified a mutation in one of the genes, FBLN3, in a disease resembling AMD.
In their study, the researchers screened the genes FBLN1, FBLN2, FBLN4, FBLN5, and FBLN6 for variations that could affect the function of the resulting fibulin proteins. To determine whether disease-causing mutations existed, they compared the patients' genes with those of control individuals who did not have AMD.
The researchers found variations in FBLN1, FBLN2, FBLN4, and FBLN6 that could have contributed to AMD, but these changes were not statistically significant in terms of their comparative occurrence in AMD patients and healthy controls.
However, the researchers found that seven of the 402 AMD patients each had a different change in the FBLN5 gene that was not found in the healthy control group. Six of these seven changes altered an amino acid in the fibulin 5 protein that has been highly conserved during evolution.
Stone believes the finding offers an important lesson about searching for genetic causes for AMD. "Fifteen years ago, we and others believed that there would be a single gene that would be responsible for a substantial percentage of AMD," he said. "This experiment suggests that in reality a significant genetic cause of AMD may affect only two percent of the total. And so, fifteen years ago if we had done an experiment with 100 people and had seen a change in one only person, it wouldn't
Contact: Jim Keeley
Howard Hughes Medical Institute