Genetic association study of age‐related macular degeneration in the Spanish population |
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| Authors: | María Brión Manuel Sanchez‐Salorio Marta Cortón Maria de la Fuente Belen Pazos Mohammad Othman Anand Swaroop Goncalo Abecasis Beatriz Sobrino Angel Carracedo for the Spanish multi‐centre group of AMD |
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| Affiliation: | 1. Genetics of Cardiovascular and Ophthalmologic Diseases, Hospital‐University Complex of Santiago (CHUS), Santiago de Compostela, Spain;2. Genomics Medicine Group, University of Santiago de Compostela, CIBERER Santiago de Compostela, Spain;3. Instituto Gallego de Oftalmología (INGO), Santiago de Compostela, Spain;4. Departments of Ophthalomology and Visual Sciences and Human Genetics, University of Michigan, Ann Arbor, Michigan, USA;5. Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA;6. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Minnesota, USA;7. National Genotyping Center (CEGEN), University of Santiago de Compostela, Santiago de Compostela, Spain |
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| Abstract: | ![]()
Acta Ophthalmol. 2011: 89: e12–e22 Abstract. Purpose: To investigate new genetic risk factors and replicate reported associations with advanced age‐related macular degeneration (AMD) in a prospective case–control study developed with a Spanish cohort. Methods: Three hundred and fifty‐three unrelated patients with advanced AMD (225 with atrophic AMD, 57 with neovascular AMD, and 71 with mixed AMD) and 282 age‐matched controls were included. Functional and tagging SNPs in 55 candidate genes were genotyped using the SNPlexTM genotyping system. Single SNP and haplotype association analysis were performed to determine possible genetic associations; interaction effects between SNPs were also investigated. Results: In agreement with previous reports, ARMS2 and CFH genes were strongly associated with AMD in the studied Spanish population. Moreover, both loci influenced risk independently giving support to different pathways implicated in AMD pathogenesis. No evidence for association of advanced AMD with other previous reported susceptibility genes, such as CST3, CX3CR1, FBLN5, HMCN1, PON1, SOD2, TLR4, VEGF and VLDLR, was detected. However, two additional genes appear to be candidate markers for the development of advanced AMD. A variant located at the 3′ UTR of the FGF2 gene (rs6820411) was highly associated with atrophic AMD, and the functional SNP rs3112831 at ABCA4 showed a marginal association with the disease. Conclusion: We performed a large gene association study in advanced AMD in a Spanish population. Our findings show that CFH and ARMS2 genes seem to be the principal risk loci contributing independently to AMD in our cohort. We report new significant associations that could also influence the development of advanced AMD. These findings should be confirmed in further studies with larger cohorts. |
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| Keywords: | ABCA4 age‐related macular degeneration ARMS2 case– control study CFH FGF2 genetic association |
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