title: The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy.
abstract: Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR.
authors.affiliation: Instituto de Oftalmobiología (IOBA-Retina Group), University of Valladolid, Valladolid, Spain ; Unidad de Medicina Molecular, Departamento de Medicina, University of Salamanca, Salamanca, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Pastor-Idoate
authors.affiliation: Unidad de Medicina Molecular, Departamento de Medicina, University of Salamanca, Salamanca, Spain ; Instituto de Investigación Biomédica de Salamanca (IBSAL) and Instituto de Biología Molecular y Celular del Cáncer (IBMCC), University of Salamanca-CSIC-SACYL, Salamanca, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Rodríguez-Hernández
authors.affiliation: Instituto de Oftalmobiología (IOBA-Retina Group), University of Valladolid, Valladolid, Spain.
authors.forename: Jimena
authors.initials: J
authors.lastname: Rojas
authors.affiliation: Instituto de Oftalmobiología (IOBA-Retina Group), University of Valladolid, Valladolid, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Fernández
authors.affiliation: Instituto de Oftalmobiología (IOBA-Retina Group), University of Valladolid, Valladolid, Spain.
authors.forename: María T
authors.initials: MT
authors.lastname: García-Gutiérrez
authors.affiliation: University of Castilla La Mancha, Vissum, Albacete, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Ruiz-Moreno
authors.affiliation: Department of Sense Organs, Medical School, 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 of 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 of 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 of Health Research (NIHR), Biomedical Research Centre, London, United Kingdom ; Nuffield Laboratory of Ophthalmology, University of Oxford, John Radcliffe Hospital Oxford, United Kingdom.
authors.forename: Robert E
authors.initials: RE
authors.lastname: MacLaren
authors.affiliation: Moorfields Eye Hospital, National Institute of Health Research (NIHR), Biomedical Research Centre, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Charteris
authors.affiliation: Rotterdam Eye Hospital, Erasmus Medical Center, University of Rotterdam, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: VanMeurs
authors.affiliation: Unidad de Medicina Molecular, Departamento de Medicina, University of Salamanca, Salamanca, Spain ; Instituto de Investigación Biomédica de Salamanca (IBSAL) and Instituto de Biología Molecular y Celular del Cáncer (IBMCC), University of Salamanca-CSIC-SACYL, Salamanca, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.affiliation: Instituto de Oftalmobiología (IOBA-Retina Group), University of Valladolid, Valladolid, Spain.
authors.forename: José C
authors.initials: JC
authors.lastname: Pastor
mesh_terms: D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D009426:Netherlands; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D006113:United Kingdom; D018630:Vitreoretinopathy, Proliferative / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2