NEW YORK (Reuters Health) - There appears to be “strong evidence” that a common haplotype in the complement regulatory gene Factor H (HF1) predisposes people to age-related macular degeneration (AMD), suggesting that this gene may be a target for therapeutic intervention.
In the May 2nd online PNAS Early Edition, Dr. Gregory S. Hageman of the University of Iowa, Iowa City and colleagues report that HF1 accumulates within drusen -- hallmark deposits associated with early AMD -- and is synthesized locally by the retinal pigment epithelium.
The team looked for genetic variations in HF1 in 900 patients with AMD and 400 matched controls and found a “highly significant association” between eight common HF1 single nucleotide polymorphisms (SNPs) and AMD.
Most of the AMD-associated HF1 SNPs lie within important functional domains of the encoded protein, they say, perhaps hampering its normal regulatory activity.
The most frequent “at-risk” haplotype was present in 50% of the subjects with AMD compared with only 29% of the controls. Homozygotes for this haplotype accounted for 24% of AMD cases and only 8% of controls.
“The magnitude of the observed association is striking when compared to those of genetic abnormalities previously linked to AMD,” the authors point out. They also identified several protective HF1 haplotypes, “further implicating HF1 function in the pathogenetic mechanisms underlying AMD.”
The researchers suggest that “genetically predetermined variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population.
Source: PNAS Early Edition 2005. [ Google search on this article ]
MeSH Headings:Biological Sciences: Biology: Genetics: Haplotypes: Macular Degeneration: Retinal Drusen: Biological SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
