Genetic association study of age-related macular degeneration in the Spanish population

Autor: Arias Barquet, Lluís, Sanchez-Salorio, Manuel, Brión, María, Cortón, Marta, Fuente, Maria de la, Pazos, Belen, Othman, Mohammad, Swaroop, Anand, Abecasis, Gonçalo R., Sobrino, Beatriz, Carracedo Álvarez, Ángel, Spanish multi-centre group of AMD
Rok vydání: 2010
Předmět:
Male
Candidate gene
genetic structures
ABCA4
Genome-wide association study
Polymerase Chain Reaction
Macular Degeneration
Risk Factors
Surveys and Questionnaires
Odds Ratio
Prospective Studies
Degeneració (Patologia)
Aged
80 and over
Genetics
Nucleotides
Degeneration (Pathology)
General Medicine
Middle Aged
Retinal diseases
Malalties de la retina
Complement Factor H
Female
Genetic Markers
Genotype
Single-nucleotide polymorphism
Biology
Genetic polymorphisms
Polymorphism
Single Nucleotide
Article
Geographic Atrophy
Humans
SNP
Genetic Predisposition to Disease
Aged
Genetic association
Polimorfisme genètic
Haplotype
Case-control study
Proteins
Choroidal Neovascularization
eye diseases
Nucleòtids
Ophthalmology
Spain
Case-Control Studies
biology.protein
sense organs
Proteïnes
Genètica
Genome-Wide Association Study
Zdroj: Dipòsit Digital de la UB
Universidad de Barcelona
ISSN: 1755-375X
DOI: 10.1111/j.1755-3768.2010.02040.x
Popis: 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 SNPlex TM 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.
Databáze: OpenAIRE
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