Cho - Toll-like Receptor Polymorphisms and Age-Related...

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Unformatted text preview: Toll-like Receptor Polymorphisms and Age-Related Macular Degeneration: Replication in Three Case–Control Samples Youngeun Cho, 1 Jie Jin Wang, 2 Emily Y. Chew, 3 Frederick L. Ferris III, 3 Paul Mitchell, 2 Chi-Chao Chan, 1 and Jingsheng Tuo 1 P URPOSE . Innate immunity appears to play a key role in age- related macular degeneration (AMD). Although two previous studies reported that gene variations in Toll-like receptor (TLR)-3 and -4 are associated with AMD, other studies have not confirmed these associations. In this study, three independent samples (two U.S. clinic-based case–control study samples and one Australian population-based study sample) were used to further assess the association of the polymorphisms rs3775291 in TLR3 and rs4986790 in TLR4 with AMD. M ETHODS . AMD cases and unrelated controls were collected from the National Eye Institute Clinical Center (NEI, n 5 320), the Age-Related Eye Disease Study (AREDS, n 5 483), and the Blue Mountains Eye Study (BMES, n 5 852). DNA extracted from subjects was genotyped for rs3775291 and rs4986790, and the associations with AMD were investigated. R ESULTS . Neither of the two polymorphisms rs3775291 and rs4986790 had a statistically significant association with AMD in any of the three sample sets or in combinations of the sets. Analysis of the combined geographic atrophy or neovascular AMD cases in the NEI, AREDS, and BMES sample sets also failed to demonstrate statistically significant asso- ciations of those two single nucleotide polymorphisms with advanced AMD. C ONCLUSIONS . Even with previously verified samples sets and adequate study powers, the results did not confirm the re- ported associations of TLR3 rs3775291 and TLR4 rs4986790 with AMD in the three independent samples, individually or combined. ( Invest Ophthalmol Vis Sci. 2009;50:5614–5618) DOI:10.1167/iovs.09-3688 A ge-related macular degeneration (AMD) is one of the most prevalent causes of severe visual impairment in the West- ern world. 1 Advanced AMD has two major subtypes: geo- graphic atrophy (GA) AMD and neovascular (NV) AMD. In GA, central vision decreases more slowly because photoreceptors and retinal pigment epithelial (RPE) cells die gradually, whereas in neovascular AMD, central vision usually deterio- rates more rapidly because of the development of choroidal neovascularization (CNV) and fluid leakage. Epidemiologic studies suggest that personal risk factors, such as age and body mass index, and environmental rick factors, such as cigarette smoking, contribute to the risk of developing advanced AMD in combination with genetic risk factors. 2–6 Various single nucleotide polymorphisms (SNPs) have been widely reported to be associated with AMD....
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This note was uploaded on 11/21/2010 for the course NUT 72880 taught by Professor Clifford during the Fall '10 term at UC Davis.

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Cho - Toll-like Receptor Polymorphisms and Age-Related...

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