title: The p53 codon 72 polymorphism (rs1042522) is associated with proliferative vitreoretinopathy: the Retina 4 Project.
abstract: OBJECTIVE
  To compare the distribution of a p53 gene polymorphism among European subjects undergoing primary retinal detachment (RD) surgery in relation to the development of proliferative vitreoretinopathy (PVR).
  
  
  METHODS
  Case-controlled gene association study conducted as a component of the Retina 4 Project (a European multicenter study).
  
  
  METHODS
  Five hundred fifty DNA samples, 134 with PVR secondary to primary RD and 416 with RD without PVR.
  
  
  METHODS
  The p53 codon 72 polymorphism (rs1042522) was analyzed using allele-specific primer polymerase chain reaction. Proportions of genotypes and the proline (Pro-P) homozygote groups between subsamples from different countries were analyzed in 2 phases. In the first, subsamples from Spain and Portugal were analyzed. After significant results were found, samples from the United Kingdom (UK) and The Netherlands were analyzed (second phase). Genotypic and allelic frequencies were compared between cases and controls in the global sample.
  
  
  METHODS
  Single significant associations with PVR.
  
  
  RESULTS
  A significant difference (P<0.05, Fisher exact test) was observed regarding the p53 genotype frequencies at codon 72 between the PVR cases and the non-PVR controls in Spain and Portugal (phase I), but not in the UK or The Netherlands (phase II). Analysis of Pro homozygote carriers between cases and controls revealed differences in Spain (29.01-42.18 and 2.29-10.20, respectively), Portugal (10.49-29.50 and 1.35-8.89, respectively), and The Netherlands (16.49-31.70 and 4.51-15.09, respectively), but no differences in the UK (7.68-18.1 and 4.85-13.94, respectively). The odds ratio of Pro carriers from Spain and Portugal together was 8.12 (95% confidence interval [CI], 3.72-17.69; P<0.05), whereas the odds ratio of Pro carriers from the UK and The Netherlands was 2.12 (95% CI, 0.96-4.68; P = 0.07). All control samples were in Hardy-Weinberg equilibrium. Considering the entire sample, significant differences were found in genotype frequencies between cases (RR, 30.59%; RP, 43.28%; PP, 26.11% [R = Arg; P = Pro]) and controls (RR, 39.66%; RP, 52.64%; PP, 7.69%) and in Pro homozygote carriers between controls (Pro homozygote 95% CI, 18.67-33.52) and cases (Pro homozygote 95% CI, 5.1-10.2).
  
  
  CONCLUSIONS
  Results indicate that the Pro variant of p53 codon 72 polymorphism is associated with a higher risk of PVR developing after a primary RD. Further studies are necessary to understand the role of this polymorphism in the development of PVR.
authors.affiliation: Department of Ophthalmology, University Hospital of Valladolid, Valladolid, Spain; Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain; Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, University of Valladolid, Valladolid, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Pastor-Idoate
authors.affiliation: Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Rodriguez-Hernández
authors.affiliation: Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, University of Valladolid, Valladolid, Spain.
authors.forename: Jimena
authors.initials: J
authors.lastname: Rojas
authors.affiliation: Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, University of Valladolid, Valladolid, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Fernández
authors.affiliation: Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, University of Valladolid, Valladolid, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: García-Gutierrez
authors.affiliation: University of Castilla la Mancha, Vissum, Albacete, Spain.
authors.forename: Jose María
authors.initials: JM
authors.lastname: Ruiz-Moreno
authors.affiliation: Department of Sense Organs, Faculty of Medicine, University of Porto, Hospital San João, Porto, Portugal.
authors.forename: Amandio
authors.initials: A
authors.lastname: Rocha-Sousa
authors.affiliation: Moorfields Eye Hospital, National Institute Health Research (NIHR), Biomedical Research Centre, London, United Kingdom.
authors.forename: Yashin
authors.initials: Y
authors.lastname: Ramkissoon
authors.affiliation: Moorfields Eye Hospital, National Institute Health Research (NIHR), Biomedical Research Centre, London, United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Harsum
authors.affiliation: Moorfields Eye Hospital, National Institute Health Research (NIHR), Biomedical Research Centre, London, United Kingdom; Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom.
authors.forename: Robert E
authors.initials: RE
authors.lastname: MacLaren
authors.affiliation: Moorfields Eye Hospital, National Institute Health Research (NIHR), Biomedical Research Centre, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Charteris
authors.affiliation: Rotterdam Eye Hospital, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: van Meurs
authors.affiliation: Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain; Instituto de Biología Molecular y Celular del Cancer (IBMCC), University of Salamanca Consejo Superior de Investigaciones Científicas (CSIC), Salamanca, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.affiliation: Department of Ophthalmology, University Hospital of Valladolid, Valladolid, Spain; Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, University of Valladolid, Valladolid, Spain. Electronic address: pastor@ioba.med.uva.es.
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Pastor
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012163:Retinal Detachment / Q000150:complications; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D018630:Vitreoretinopathy, Proliferative / Q000209:etiology / Q000235:genetics* / Q000601:surgery
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53