title: Genetic association study of age-related macular degeneration in the Spanish population.
abstract: OBJECTIVE
  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™ 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hospital-University Complex of Santiago, Santiago de Compostela, Spain. maria.brion@usc.es
authors.forename: María
authors.initials: M
authors.lastname: Brión
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Salorio
authors.forename: Marta
authors.initials: M
authors.lastname: Cortón
authors.forename: Maria
authors.initials: M
authors.lastname: de la Fuente
authors.forename: Belen
authors.initials: B
authors.lastname: Pazos
authors.forename: Mohammad
authors.initials: M
authors.lastname: Othman
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.forename: Goncalo
authors.initials: G
authors.lastname: Abecasis
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sobrino
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D020256:Choroidal Neovascularization / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D057092:Geographic Atrophy / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D013030:Spain; D011795:Surveys and Questionnaires
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D005819:Genetic Markers; D011506:Proteins; D017242:Complement Factor H