title: Further associations between mutations and polymorphisms in the ABCA4 gene: clinical implication of allelic variants and their role as protector/risk factors.
abstract: OBJECTIVE
  Mutations in ABCA4 have been associated with autosomal recessive Stargardt disease, autosomal recessive cone-rod dystrophy, and autosomal recessive retinitis pigmentosa. The purpose of this study was to determine (1) associations among mutations and polymorphisms and (2) the role of the polymorphisms as protector/risk factors.
  
  
  METHODS
  A case-control study was designed in which 128 Spanish patients and 84 control individuals were analyzed. Patient samples presented one or two mutated alleles previously identified using ABCR400 microarray and sequencing.
  
  
  RESULTS
  A total of 18 previously described polymorphisms were studied in patients and control individuals. All except one presented a polymorphisms frequency higher than 5% in patients, and five mutations were found to have a frequency >5%. The use of statistical methods showed that the frequency of the majority of polymorphisms was similar in patients and controls, except for the IVS10+5delG, p.Asn1868Ile, IVS48+21C>T, and p.Arg943Gln polymorphisms. In addition, IVS48+21C>T and p.Arg943Gln were found to be in linkage disequilibrium with the p.Gly1961Glu and p.Arg602Trp mutations, respectively.
  
  
  CONCLUSIONS
  Although the high allelic heterogeneity in ABCA4 and the wide spectrum of many common and rare polymorphisms complicate the interpretation of clinical relevance, polymorphisms were identified that may act as risk factors (p.Asn1868Ile) and others that may act as protection factors (p.His423Arg and IVS10+5 delG).
authors.affiliation: Genetics Department, Fundacion Jimenez Diaz-CIBERER, Madrid, Spain. jaguirre@fjd.es
authors.forename: Jana
authors.initials: J
authors.lastname: Aguirre-Lamban
authors.forename: Juan José
authors.initials: JJ
authors.lastname: González-Aguilera
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.forename: Diego
authors.initials: D
authors.lastname: Cantalapiedra
authors.forename: Almudena
authors.initials: A
authors.lastname: Avila-Fernandez
authors.forename: Cristina
authors.initials: C
authors.lastname: Villaverde-Montero
authors.forename: Marta
authors.initials: M
authors.lastname: Corton
authors.forename: Fiona
authors.initials: F
authors.lastname: Blanco-Kelly
authors.forename: Blanca
authors.initials: B
authors.lastname: Garcia-Sandoval
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D004585:Electrooculography; D004596:Electroretinography; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D012307:Risk Factors; D017385:Sequence Homology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters