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Gene Found to Increase Risk of the Most Common Cause of Blindness
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March 10, 2005
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<a href="/about/news-and-events/news?topic=246" hreflang="en">Age-Related Macular Degeneration</a>
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<p>Investigators have identified a gene that is “strongly associated” with a person’s risk for developing age-related macular degeneration (AMD). The finding was made by four independent teams, which include researchers with the National Eye Institute (NEI) and the National Cancer Institute, components of the National Institutes of Health (NIH), and other leading research centers. Detecting an AMD-associated gene may lead to early detection and new strategies for prevention and treatment for the debilitating eye disease. Papers from three independent teams appear in the April 15 issue of the journal Science, with a fourth paper published in the May 3 issue of the Proceedings of the National Academy of Sciences (PNAS). AMD is a disease that blurs or destroys sharp, central vision and is the leading cause of blindness in people over age 60. There is no known cure for AMD. Most scientists think the cause lies in a complex interplay of hereditary and environmental factors.</p>
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<img src="https://www.nei.nih.gov/sites/default/files/styles/small/public/2021-08/chf_large.jpeg?itok=dMPeLKU2" alt="In this tissue section of the human retina, bright green demonstrates the presence of the protein product of CFH gene. A variant form of the CFH gene increases the risk for age-related macular degeneration." width="542" height="551">
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<p>Family history of AMD is a risk factor for the disease. In recent years, researchers have been applying several genome-derived experimental approaches to find AMD-associated genes. The new studies provide the strongest evidence yet of a role for common genetic variants in the development of AMD.</p><p>“The four studies are a significant step in AMD research. They confirm a strong genetic component of AMD, which may allow scientists to develop tests for the disease before symptoms begin to appear and when therapies might help slow its progress,” said Paul A. Sieving, M.D., Ph.D., director of the National Eye Institute.</p><p>The four studies described in Science and PNAS used distinct but complementary methods to screen the genomes from non-overlapping groups of AMD patients. Yet all four studies came up with a commonly inherited variant of the same gene, called complement factor H (CFH). The CFH gene produces a protein that helps regulate inflammation in part of the immune system that attacks diseased and damaged cells.<br>“This exciting work helps clarify how AMD develops and the relationship of the immune system with the disease. This could lead to entirely new approaches for therapeutics,” said Emily Chew, M.D., deputy director, NEI Division of Epidemiology and Clinical Research, and collaborator on one of the studies.</p><p>Dr. Chew’s team, headed by Josephine Hoh, Ph.D., Yale School of Public Health, New Haven, CT, found that people whose genetic makeup includes a variant of the CFH gene are 7.4 times more likely to develop AMD. The study was based on whole genome analysis of participants from the NEI-sponsored Age-Related Eye Disease Study, a major clinical study that closely followed nearly 5,000 patients with varying stages of AMD.</p><p>The team will next look at a larger number of patients and perhaps look at genetic differences between patients with the wet and dry forms of AMD. Wet AMD occurs when abnormal blood vessels behind the retina start to grow under the macula, a part of the central retina, where light is converted to nerve signals to the brain. Loss of central vision can be rapid. Dry AMD occurs when the light-sensitive cells in the macula slowly break down. Central vision can be lost gradually.</p><p>The second team, headed by Jonathan L. Haines, Ph.D. and Margaret A. Pericak-Vance, Ph.D., Vanderbilt University Medical Center, Nashville, identified the CFH gene by using high resolution mapping of a portion of a chromosome that had previously been associated with AMD in family studies.</p><p>A third research team, also funded by NEI, was headed by Albert O. Edwards, M.D., the University of Texas Southwestern Medical Center, Dallas.<br>An international research team jointly led by Gregory Hageman at the University of Iowa and Rando Allikmets of Columbia University College of Physicians and Surgeons conducted the work reported in PNAS Dr. Hageman and a team of researchers from UC Santa Barbara have been investigating the possible connection of AMD with an immune mechanism for several years.</p><p># # #</p><p><strong>Journal Citations:</strong></p><p>Complement factor H mutation in the advanced form of age-related macular degeneration. Klein, R.J., et. al.<em> Science Express,</em> 10 March 2005; 10.1126/science.1109557</p><p>Complement factor H variant increases the risk of age-related macular degeneration. Haines, J.L., et. al. <em>Science Express,</em> 10 March 2005; 10.1126/science.1110359</p><p>Complement factor H polymorphism and age-related macular degeneration. Edwards, A.O., et. al. <em>Science Express,</em> 10 March 2005; 10.1126/science.1110189</p><p>A Common Haplotype in the Complement Regulatory Gene, Factor H (HF1/CFH), Predisposes Individuals to Age-related Macular Degeneration. Hageman, G.S., et. al.,<br><em>Proc. Natl. Sci. Acad.</em> USA, 2 May 2005; 102 (18).</p><p># # #</p><h3>Citations</h3><ul><li>Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, Pericak-Vance MA. Complement Factor H Variant Increases The Risk of Age-Related Macular Degeneration. <em>Science</em>. 2005 Mar 10. [Epub ahead of print]. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15761120">PubMed</a></li><li>Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J. Complement Factor H Polymorphism in Age-Related Macular Degeneration. <em>Science</em>. 2005 Mar 10. [Epub ahead of print] <a href="http://www.ncbi.nlm.nih.gov/pubmed/15761122">PubMed</a></li><li>Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complete Factor H Polymorphism And Age-Related Macular Degeneration. <em>Science</em>. 2005 Mar 10. [Epub ahead of print]. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15761121">PubMed</a></li><li>Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R. A Common Haplotype in The Complement Regulatory Gene Factor H (HF1/CFH) Predisposes Individuals to Age-Related Macular Degeneration. <em>Proc Natl Acad Sci U S A.</em> 2005 May 3. [Epub ahead of print]. <a href="https://pubmed.ncbi.nlm.nih.gov/15870199/">PubMed</a></li></ul>
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