The GG genotype of erythropoietin rs1617640 polymorphism affects the risk of proliferative diabetic retinopathy in Slovenian subjects with type 2 diabetes mellitus: enemy or ally?

Abstract

Purpose: The aim of this study was to investigate the relationship between erythropoietin rs1617640 polymorphism and proliferative diabetic retinopathy (PDR) in Slovenian subjects with type 2 diabetes mellitus. The second aim was to find whether erythropoietin expression in fibrovascular membranes varies among individuals carrying different genotypes of the rs1617640. Methods: This was a retrospective cross-sectional study based on 797 unrelated Slovenian (Caucasian) participants with type 2 diabetes mellitus. The study group consisted of 217 cases with PDR and 580 controls without clinical signs of diabetic retinopathy. Each subject was genotyped for rs1617640 polymorphism. Fibrovascular membranes from 27 subjects who underwent vitreoretinal surgery were analysed with immunohistochemistry. We searched for expression of erythropoietin, its cognate receptor and for a pan-endothelial marker CD-34. Results: Our results show that subjects carrying a minor GG genotype had significantly higher risk for PDR in both unadjusted (p = 0.02) and adjusted (p = 0.04) recessive genetic models. Subjects with the GG genotype had a 1.6-fold increased risk of developing PDR compared to subjects carrying the major T allele. In fibrovascular membranes from subjects with PDR, the mean number of cells expressing EPO was significantly higher in G allele carriers compared to the homozygotes for the common T allele. Conclusion: In Slovenian subjects with type 2 diabetes mellitus, a significant increased risk of PDR was found in GG carriers of the erythropoietin gene rs1617640 polymorphism.