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Salvador Pastor, Irene Rodriguez-Hernandez, Jimena Rojas Spano, Rogelio Gonzalez-Sarmiento, Jose-Carlos Pastor, Genetics on PVR Study Group; Distribution of MDM2 T309G polymorphism in European patients with Proliferative Vitreoretinopathy. Retina 4 project. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6257.
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Our group has recently reported a significant association between p53 and Proliferative Vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RD). Murine double minute 2 (MDM2) gene codes for a protein that plays an important role as negative regulator of p53. The aim of this study has been to assess the distribution of MDM2 T309G genotypes among a series of patients suffering primary RD and secondary PVR.
As a component of the Retina 4 project (European multicentric study for analysing the genetic component of PVR) 555 DNA samples from patients with PVR (n:134) secondary to a primary RD (cases) and Non PVR (n:421) (controls) were analyzed for the MDM2 T309G polymorphism (rs2279744) using allele specific primer PCR. Genotypic and allelic frequencies were compared between cases and controls. The proportions of genotypes between sub-samples from different countries were analyzed.
Significant differences (p<0.05, Fisher test) were observed regarding the MDM2 genotype frequencies at position 309 of intron 1 between the PVR cases (GG: 21.6%, TG: 54.5%, TT: 23.9 %) and controls (GG: 7.4%, TG: 43.9%, TT: 48.7%) and in G homozygote carriers between controls (95% CI G homozygote: 26.3 to 32.4) and cases (95% CI G homozygote: 42.9 to 54.9). The odd ratio of G carriers was 5.9 (95% CI: 3.2 to 11.2). The comparison of proportions of genotypes between sub-samples from different countries showed also significant differences between cases and controls. Distribution of G homozygote carriers between cases and controls revealed differences in Spain [35.1-53.0]/[22.6-32.9], Portugal [38.9-74.4]/[21.4-38.9], Holland [40.6-66.3]/[25.3-38.8] and also in UK [37.5-62.4]/[23.3-34.2]. The odds ratio of G carriers from Spain and Portugal was 5.4 (95% Confidence Interval (CI):2.3-12.7; p<0.05), whereas the odds ratio of G carriers from UK and Holland was 7.3 (95%CI: 2.8-19.1; p<0.05 ). All control samples were in Hardy-Weinberg equilibrium.
Our results suggest that the G allele of MDM2 SNP309 polymorphism is associated with a higher risk of developing PVR after a primary RD. Further studies are necessary to know if a down-regulation in the p53 tumor suppressor pathway could be an important key in developing of PVR. These findings could open new therapeutic targets in the prophylaxis of PVR.
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