Identification of new candidate genes for retinopathy in type 2 diabetics. Valencia Study on Diabetic Retinopathy (VSDR). Report number 3

Abstract Objective To identify genes involved in the pathogenic mechanisms of non-proliferative diabetic retinopathy (NPDR), among which include oxidative stress, extracellular matrix changes, and/or apoptosis, in order to evaluate the risk of developing this retinal disease in a type 2 diabetic (DM2) population. Material and methods A case–control study was carried out on 81 participants from the Valencia Study on Diabetic Retinopathy (VSDR) of both genders, with ages 25–85 years. They were classified into: (i) DM2 group (n = 49), with DR (+DR; n = 14) and without DR (−DR; n = 35), and (ii) control group (GC; n = 32). The protocols included a personal interview, standardized ophthalmological examination, and blood collection (to analyze the DNA for determining the gene expression ( TP53 , MMP9 , and SLC23A2 ) in the study groups). Statistical analyses were performed using the SPSS v22.0 program. Results The TP53 and MMP9 genes showed a higher expression in the DM2 group compared to the GC, although the difference was only significant for the MMP9 gene ( TP53 : 10.40 ± 1.20 vs. 8.23 ± 1.36, p  = 0.084; MMP9 : 1.45 ± 0.16 vs. 0.95 ± 0.16, p  = 0.036), and the SLC23A2 gene showed a significant lower expression in the DM2 vs. CG (5.58 ± 0.64 vs. 11.66 ± 1.90, p  = 0.026). When sub-dividing the DM2 group according to the presence of retinopathy, the expression of the TP53 , MMP9 and SLC23A2 genes showed significant differences between the DM2−RD, DM2+RD and GC groups ( TP53 : 9.95 ± 1.47 vs. 11.52 ± 2.05 vs. 8.23 ± 1.36, p  = 0.038; MMP9 : 1.47 ± 0.20 vs. 1.41 ± 0.27 vs. 0.95 ± 0.16, p  = 0.021; SLC23A2 : 5.61 ± 0.77 vs. 5.51 ± 1.21 vs. 11.66 ± 1.90, p  = 0.018). Conclusions Genes involved in extracellular matrix integrity ( MMP9 ) and/or apoptosis ( TP53 ), could be considered potential markers of susceptibility to the development/progression of NPDR. Interestingly, the SLC232A2 gene (ascorbic acid transporter) can be considered a protector of the risk of the development/progression of the retinopathy.