MiR-9-3 hypermethylation is associated with stages of diabetic retinopathy.

Purpose: To investigate the potential relation between methylation of miR-9-3 and stages of diabetic retinopathy (DR). Additionally, we explored whether miR-9-3 methylation impacts the serum levels of Vascular Endothelial Growth Factor (VEGF).

Methods: A cross-sectional study was conducted with 170 participants with type 2 diabetes, including a control group ( = 64) and a diabetes retinopathy group ( = 106), which was further divided into NPDR ( = 58) and PDR ( = 48) subgroups. Epidemiological, clinical, anthropometric, biochemical ELISA assay were analysed. DNA extracted from leukocytes was used to profile miR-9-3 methylation using PCR-MSP.

Results: MiR-9-3 hypermethylated profile was higher in the DR group ( < 0.001) and PDR subgroup compared to DM2 control group ( < 0.001). The hypermethylated profile in the PDR subgroup was also higher compared to NPDR subgroup ( < 0.001). There was no difference between DM2 control and NPDR group ( = 0.234). Logistic regression showed that miR-9-3 hypermethylation increases the odds of presenting DR (OR: 2.826;  = 0.002) and PDR (OR: 5.472;  < 0.001). In addition, hypermethylation of miR-9-3 in the DR and NPDR subgroup was associated with higher serum VEGF-A levels ( = 0.012 and  = 0.025, respectively).

Conclusion: The methylation profile of the miR-9-3 promoter increases the risk of developing PDR. Higher levels of VEGF-A are associated with miR-9-3 hypermethylated profile in patients in the DR and NPDR stages.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01411-9.