title: BAX and BCL-2 polymorphisms, as predictors of proliferative vitreoretinopathy development in patients suffering retinal detachment: the Retina 4 project.
abstract: OBJECTIVE
  To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal detachment (RRD) surgery in relation to the further development of proliferative vitreoretinopathy (PVR).
  
  
  METHODS
  A case-control gene association study, as a part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms were analysed in 555 samples from patients with RRD (134 with PVR secondary to surgery). Proportions of genotypes and AA homozygous groups of BCL-2 and BAX polymorphisms between subsamples were analysed in two phases. Genotypic and allelic frequencies were compared in global sample and in subsamples.
  
  
  RESULTS
  BAX: Differences were observed in the genotype frequencies and in AA carriers between controls and cases in the global series. The odds ratio (OR) of A carriers in the global sample was 1.7 (95% CI: 1.23-2.51). Proportions of genotypes in Spain + Portugal were significant different. The OR of A carriers from Spain and Portugal was 1.8 (95% CI: 1.11-2.95). BCL-2: No significant differences were observed in genotype frequencies. However, proportions of genotypes in Spain + Portugal were significant. A protective effect (OR: 0.6 95% CI: 0.43-0.96) was found in A carriers from Spain and Portugal.
  
  
  CONCLUSIONS
  Results suggest that A allele of rs4645878 could be a biomarker of high risk of developing PVR in patients undergoing RD surgery. The possible role of BCL-2 (inhibitor of necroptosis pathway) as a possible new target in PVR prophylaxis should be investigated.
authors.affiliation: Instituto de Oftalmobiología Aplicada (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 Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Investigación Biomédica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Rodríguez-Hernández
authors.affiliation: Instituto de Oftalmobiología Aplicada (IOBA-Retina Group), University of Valladolid, Valladolid, Spain.
authors.forename: Jimena
authors.initials: J
authors.lastname: Rojas
authors.affiliation: Instituto de Oftalmobiología Aplicada (IOBA-Retina Group), University of Valladolid, Valladolid, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Fernández
authors.affiliation: Instituto 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, Albacete, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ruiz-Moreno
authors.affiliation: Department of Sense Organs, Medical School, Hospital SanJoão, University of Porto, 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, UK.|Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK.
authors.forename: Yashin D
authors.initials: YD
authors.lastname: Ramkissoon
authors.affiliation: Moorfields Eye Hospital, National Institute of Health Research (NIHR), Biomedical Research Centre, London, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Harsum
authors.affiliation: Moorfields Eye Hospital, National Institute of Health Research (NIHR), Biomedical Research Centre, London, UK.|Nuffield Laboratory of Ophthalmology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
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, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: Charteris
authors.affiliation: Rotterdam Eye Hospital, Erasmus Medical Center, University of Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Van Meurs
authors.affiliation: Unidad de Medicina Molecular, Departamento de Medicina, University of Salamanca, Salamanca, Spain.|Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Investigación Biomédica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.affiliation: Instituto de Oftalmobiología Aplicada (IOBA-Retina Group), University of Valladolid, Valladolid, Spain.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Pastor
mesh_terms: D000328:Adult; D017209:Apoptosis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012163:Retinal Detachment / Q000235:genetics* / Q000601:surgery; D012307:Risk Factors; D014821:Vitrectomy; D018630:Vitreoretinopathy, Proliferative / Q000175:diagnosis / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: C494826:BAX protein, human; D005819:Genetic Markers; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
keywords: Bcl-2; apoptosis; bax; necroptosis; proliferative vitreoretinopathy; retinal detachment