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G. J. McKay, G. Silvestri, S. Dasari, U. Chakravarthy, A. E. Hughes; Elucidation of Light Associated Age Related Macular Degeneration Genetic Risk Loci. Invest. Ophthalmol. Vis. Sci. 2008;49(13):241. doi: https://doi.org/.
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Light has been implicated as a risk factor for Age Related Macular Degeneration (AMD). This study tests for genetic association between genes involved in light transduction and AMD.
Venous blood samples (6ml) were collected from patient samples (n=300) with documented end-stage neovascular AMD, a replicate cohort of end-stage neovascular AMD (n=300) and an age and sex-matched control cohort (n=250). All patients underwent full ophthalmic examination and participated in a short questionnaire to detail history of smoking, micro and macro angiopathic disease, drug history, refractive status, eye colour, body mass index and family history. Genetic haplotype analysis was undertaken for several chosen candidate genes from pooled DNA samples previously processed on Illumina 317k SNP chips. Haplotypic structure was determined using information derived from the HapMap project for each of the candidates. Genotyping was undertaken on a multiplexed SNaPshot technology platform (ABI).
Fourteen SNPs across 2 genes were genotyped in the case and control cohorts. Results indicate a novel association between neovascular AMD and a gene that is involved in light transduction with a common variant of this gene increasing the risk (odds ratio of 1.58, p<0.003). Evaluation of the strength of this association is ongoing in a replicate cohort.
Our results show that this simple multiplex analysis can quickly determine the haplotypic structure across a number of potential disease-associated loci. Light energy has been considered a risk factor for AMD but the evidence of a causal link is inconsistent with some studies indicating an adverse association and others no association. Within the visible spectrum blue wavelengths are the cause of most damage and this has been demonstrated at a cellular level to be proportional to the duration of exposure (Sparrow et al., 2002). New data from the EUREYE study which recruited some 5000 participants from 7 European countries recently revealed that the risk of neovascular AMD is elevated 4-fold in those people who fell into the highest quintile of blue light exposure and the lowest quintile of serum antioxidants suggesting a strong association (Fletcher et al., in press). Genetic evidence demonstrating association between a gene involved in the processing of light and AMD further strengthens the hypothesis that increased light exposure in some people can increase their lifetime risk to neovascular AMD.Sparrow et al. Invest Ophthalmol Vis Sci 2002; 43:1222-1227.Fletcher et al. Arch Ophthalmol. 2007; In press.
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