BAX and BCL-2 genes in patients with Retinal Detachment with and without Proliferative Vitreoretinopathy. The Retina 4 project

Purpose To compare the distribution of BAX G(-248)A and BCL-2 C(-938)A genotypes among European subjects undergoing rhegmatogenous retinal detachment surgery in relation to further development of proliferative vitreoretinopathy (PVR). Methods A case-control gene association study as part of the Retina 4 Project was designed. Two promoter single nucleotide polymorphisms (rs2279115 and rs4645878) were analysed by TaqMan 5'exonuclease allelic discrimination assay, using a StepOne® system in 134 samples from patients with PVR and 421 without PVR. Proportions of genotypes and AA homozygote groups of these polymorphisms were analysed. Genotypic and allelic frequencies were compared in global sample and in sub-samples. Results BAX gene: In the comparison of proportions of genotypes in Spain, Spain+Portugal and in the global sample, significant differences were found. The odds ratio (OR) for A carriers in Spain and Spain+Portugal was 1.8, and 1.7 in the global sample. BCL-2 gene: Significant differences were observed regarding proportions of genotypes in Spain+Portugal. Furthermore, a protective effect was found in the analysis of A carriers from Spain+Portugal with an OR of 0.6. Conclusion The A allele of BAX is associated with a higher risk of developing PVR, suggesting that a down-regulation in the apoptosis pathway could be an important key in PVR pathogenesis. Additionally, the role of BCL-2 gene (inhibitor of necroptosis pathway) is proposed as a possible new target in PVR prophylaxis.