Salt Lake City-Population studies in Utah and Iceland have identified a gene variant that is associated with an increased risk of a precursor of age-related macular degeneration (AMD), researchers report.
Previous studies by several groups have suggested that a gene in a particular part of chromosome 1 is linked to the chance of getting AMD, said Kang Zhang, MD, PhD, of the University of Utah Moran Eye Center, one of the senior authors of a report on the genetic studies published by the Public Library of Science, who led the University of Utah team. The gene codes for a protein, complement factor H (CFH), that is involved in controlling one part of the immune system.
"This gene is involved in the immune response for defense against infection," Dr. Zhang said. "It can go haywire and contribute to the development of AMD."
One part of the study, done in Iceland, obtained genotypes on 581 patients with advanced AMD-278 with the wet form of the condition, 203 with the dry form, and 100 with mixed wet/dry-and 435 with early AMD. Of those with early AMD, 220 had drusen. Both soft confluent drusen, which have been shown to contain inflammatory modulators, and pigmentary abnormalities of the retinal pigment epithelium (RPE) are considered to be early indicators of risk of developing advanced AMD.
Another part of the study, done in Utah, obtained genotypes of 322 patients with advanced AMD-244 with the wet form, 78 with the dry form-and 109 patients with early AMD defined as having soft confluent drusen.
In both studies, the presence of the CFH Y402H variant was associated with more than a doubled risk of developing both soft confluent drusen and advanced AMD.
But presence of the gene variant is not an absolute indicator of eventual advanced AMD, Dr. Zhang said, and that finding holds clinical possibilities for prevention of visual loss due to AMD.
"Only a percentage of patients with soft confluent drusen have progression to advanced AMD; it is likely that there are other important genes yet to be found that contribute to the risk of progression to advanced AMD, especially among those who already have soft confluent drusen," he said. "If we could stop the progression in the soft confluent drusen stage without visual loss, that would almost be equivalent to a cure. In the near future, the goal is to identify, through genetic testing, patients who are at high risk of progression while the disease is at the soft confluent drusen stage, and stop the progression by pharmacologic intervention and lifestyle changes."
In addition to the University of Utah, other investigators contributing to the new findings are from deCODE Genetics, in Reykjavik, Iceland; the Department of Ophthalmology and Department of Geriatrics, National University Hospital, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik; Zhongshan Ophthalmic Center, Sun Yat-Sen University, Gaung Zhou, China; Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, China.