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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2010-04-19T00:00:00-04:00" class="date-display-single">April 19, 2010</span></p><div class='syndicate'><h1>Cholesterol Genes Tied to Age-Related Macular Degeneration</h1><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2010/20100419-eye.jpg?itok=Ozm7AieN&timestamp=1433939949 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2010/20100419-eye.jpg?itok=XQeej4jG&timestamp=1433939949" alt="Illustration of an eye with AMD deposits" title="Illustration of an eye with AMD deposits" />
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</picture><span class="caption">In AMD, small yellowish deposits made partly of cholesterol form under the retina, blurring the sharp central area of vision.</span><span class="credit">NEI</span></div>
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</div><p>A large genetic study has identified 3 new genes associated with the blinding eye disease age-related macular degeneration (AMD). Two of the genes are involved in the cholesterol pathway—a formerly unknown biological pathway for AMD disease development. The finding suggests new treatment and prevention approaches.</p>
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<p>AMD gradually destroys sharp, central vision as a person ages. It is a leading cause of visual impairment and blindness in older Americans. Genome-wide association studies (GWAS) have previously uncovered genes linked to AMD risk. In these studies, researchers scan the entire human genome looking for genetic variations between people with AMD and matched controls.</p>
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<p>The larger the GWAS, the greater its ability to uncover more genes. For the new study, Drs. Anand Swaroop of NIH's National Eye Institute (NEI) and Goncalo Abecasis at the University of Michigan, Ann Arbor, led a team that analyzed the genomes of more than 18,000 people. NEI provided partial support for the research.</p>
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<p>The team reported in the online early edition of <em>Proceedings of the National Academy of Sciences</em> on April 12, 2010, that the strongest genetic association was in a region on chromosome 22, near a gene called metalloproteinase inhibitor 3 (TIMP3). The TIMP3 gene was previously tied to Sorsby's fundus dystrophy, a rare inherited early-onset form of macular degeneration. Although further research is needed, the researchers suspect that the region in question influences the gene's expression.</p>
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<p>The study also uncovered 2 genes associated with AMD risk in the high-density lipoprotein (HDL) cholesterol pathway: human hepatic lipase (LIPC) and cholesterol ester transfer protein (CETP). Two more genes in the cholesterol pathway—lipoprotein lipase (LPL) and ATP binding cassette transporter 1 (ABCA1)—showed some association with AMD, but more research will be needed to confirm the finding.</p>
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<p>In the same edition of <em>Proceedings of the National Academy of Sciences</em>, another research team reported finding a link between AMD and LIPC in a separate GWAS effort funded in part by NEI. That team—led by Johanna M. Seddon at Tufts University Medical School and Mark Daly at Massachusetts General Hospital and the Broad Institute—also found weak associations with other HDL genes. The team was able to visualize the LIPC protein within monkey retinas as well.</p>
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<p>HDLs are among a family of lipoproteins that transport essential fats, such as cholesterol, through the bloodstream. They are known to play a role in heart disease. One hallmark of AMD is the appearance of drusen—deposits of protein, cholesterol and other lipids—under the retinal pigment epithelium, a layer of cells at the back of the eye. However, the relationship between HDL cholesterol levels in the blood and AMD is still unclear.</p>
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<p>"We suspect that these genetic variations found in the cholesterol pathway impact the retina differently from the circulatory system, so cholesterol levels in the blood may not provide meaningful information about AMD risk," Swaroop says. "Nonetheless, we have uncovered a major biochemical pathway that may be a target for future AMD treatments."</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="http://www.nei.nih.gov/health/maculardegen/index.asp" target="_top">Age-Related Macular Degeneration (AMD)</a></li></ul>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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