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Genetics important in age-related macular degeneration
Mar 15, 2005, 01:57, Reviewed by: Dr.
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"Genetic factors play a substantial role in the etiology [the cause of a disease] of AMD and associated macular characteristics, explaining 46 to 71 percent of the variation in the overall severity of the disease"
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By JAMA,
Genes play a substantial role in the development of age-related macular degeneration (AMD), one of the leading causes of irreversible blindness among older individuals, according to an article in the March issue of Archives of Ophthalmology, one of the JAMA/Archives journals.
About ten million people in the United States have signs of AMD, two million with decreased vision related to advanced AMD and eight million with earlier stages of the disease, according to background information in the article. Despite the public health impact of AMD, however, the relative roles of genes and environment in the development of AMD remain unclear. The authors state that classic twin studies, which compare the occurrence of a trait or disease in monozygotic (MZ, commonly called identical) twins versus dizygotic (DZ, commonly called fraternal) twins provide one of the most powerful methods for determining heritability (the relative contribution of genes versus environment).
Johanna M. Seddon, M.D., Sc.M., of Harvard Medical School, Boston, and colleagues surveyed 840 male twins from the National Academy of Sciences-National Research Council World War II Veteran Twin Registry born between 1917 and 1927. Two hundred and ten MZ and 181 DZ complete twin pairs and 58 singletons, whose twin were no longer living or were unavailable for the study, completed a survey and underwent an examination for AMD. The results were then statistically analyzed to determine the relative roles of genes, common shared environment and specific (unique to the individual) environment.
Of the 840 twins, 331 had no signs of macular degeneration, 241 had early signs, 162 had intermediate AMD and 106 had advanced AMD, the researchers found. There were no differences in the prevalence rates of AMD in MZ versus DZ twins. There were differences in whether the severity of AMD was the same for both twins depending on whether the twins were identical or fraternal, however. "Among pairs in which one or both twins had AMD, 55 percent of MZ pairs were classified as concordant (at the same level of severity) whereas 25 percent of DZ pairs were concordant for AMD�," the authors write. "For advanced disease�, the corresponding concordance rates were 18 percent for MZ twin pairs and 6 percent for DZ twin pairs."
"Genetic factors play a substantial role in the etiology [the cause of a disease] of AMD and associated macular characteristics, explaining 46 to 71 percent of the variation in the overall severity of the disease," the researchers found. "Environmental factors unique to each twin were estimated to account for 19 to 37 percent of the variation in AMD grade [level of severity] � and 28 to 64 percent of the variation in the specific macular measures."
"In summary, based on what is, to our knowledge, the largest twin study of AMD to date and the only population based twin registry in the United States among elderly individuals, we quantified substantial genetic influences on AMD, contributed new information about the heritability of advanced AMD, and established an important environmental contribution," the authors conclude. "This twin study underscores the need for a multifactorial approach that incorporates genetic, environmental, and biologic factors in the study of the pathogenesis and clinical management of this increasingly prevalent cause of blindness." 
- Arch Ophthalmol. 2005; 123:321-327
www.jama.com
This study was funded by grants from the National Institutes of Health, Bethesda, Md.; the Foundation Fighting Blindness Inc., Owings Mills, Md.; the Retirement Research Foundation, Chicago; the Massachusetts Lions Eye Research Fund Inc., Northboro, Mass.; and the Epidemiology Unit Research fund, the Massachusetts Eye and Ear Infirmary, Boston.
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