title: Relevance of complement factor H-related 1 (CFHR1) genotypes in age-related macular degeneration.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) has a strong genetic component with a major locus at 1q31, including the complement factor H (CFH) gene. Detailed analyses of this locus have demonstrated the existence of one SNP haplotype block, carrying the CFH 402His allele, which confers increased risk for AMD, and two protective SNP haplotypes, one of them carrying a deletion of the CFHR1 and CFHR3 genes (ΔCFHR3-CFHR1). The purpose of these studies was to evaluate the contribution of newly described CFHR1 alleles to the association of the 1q31 locus with AMD.
  
  
  METHODS
  Two hundred fifty-nine patients and 191 age-matched controls of Spanish origin were included in a transversal case-control study using multivariate logistic regression analysis and ROC (receiver operating characteristic) statistics to generate and test models predictive of the development of AMD.
  
  
  RESULTS
  This study showed for the first time that a particular CFHR1 allotype, CFHR1*A, is strongly associated with AMD (odds ratio, 2.08; 95% confidence interval, 1.59-2.73; P<0.0001) and illustrate a peculiar genotype-phenotype correlation between the CFHR1 alleles and different diseases that may have important implications for understanding the pathophysiology of AMD. It also shows that CFHR1*A is in strong linkage disequilibrium with the CFH 402His allele, which provides additional candidate variants within the major risk haplotype at 1q31, promoting its association with AMD. Further, using the Spanish population as a model, the results showed that analysis of the CFHR1 genotypes provide sufficient information to delineate the individual risk of developing AMD.
  
  
  CONCLUSIONS
  The results support a relevant role of CFHR1 in the pathogenesis of AMD.
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CSIC) and Ciber de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Martínez-Barricarte
authors.forename: Sergio
authors.initials: S
authors.lastname: Recalde
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernández-Robredo
authors.forename: Isabel
authors.initials: I
authors.lastname: Millán
authors.forename: Leticia
authors.initials: L
authors.lastname: Olavarrieta
authors.forename: Antonio
authors.initials: A
authors.lastname: Viñuela
authors.forename: Julián
authors.initials: J
authors.lastname: Pérez-Pérez
authors.forename: Alfredo
authors.initials: A
authors.lastname: García-Layana
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodríguez de Córdoba
mesh_terms: D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003176:Complement C3 / Q000235:genetics; D003180:Complement C3b Inactivator Proteins / Q000235:genetics*; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012372:ROC Curve; D012307:Risk Factors; D013030:Spain; D044465:White People / Q000235:genetics
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D011506:Proteins; D017242:Complement Factor H; D011415:Complement Factor B