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

Bruno Rafael Virginio de Sousa; Alexandre Sérgio Silva; Caroline Severo de Assis; Tainá Gomes Diniz; Marina Gonçalves Monteiro Viturino; Isabella Wanderley de Queiroga Evangelista; Luiz Henrique Agra Cavalcante-Silva; Tatjana Souza Lima Keesen; Naila Francis Paulo de Oliveira; Darlene Camati Persuhn

doi:10.1007/s40200-024-01411-9

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

J Diabetes Metab Disord. 2024 Apr 18;23(1):1189-1198. doi: 10.1007/s40200-024-01411-9. eCollection 2024 Jun.

Affiliations

¹ Post-Graduate Program in Nutrition Science, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil.
² Department of Physical Education, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil.
³ Ophthalmology, Otolaryngology and Oral and Maxillofacial Surgery Unit, Lauro Wanderley University Hospital, Federal University of Paraiba, Paraiba, Brazil.
⁴ Center of Biotechnology, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil.
⁵ Department of Molecular Biology, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil.

PMID: 38932799
PMCID: PMC11196486 (available on 2025-04-18)
DOI: 10.1007/s40200-024-01411-9

Abstract

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 (n = 64) and a diabetes retinopathy group (n = 106), which was further divided into NPDR (n = 58) and PDR (n = 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 (p < 0.001) and PDR subgroup compared to DM2 control group (p < 0.001). The hypermethylated profile in the PDR subgroup was also higher compared to NPDR subgroup (p < 0.001). There was no difference between DM2 control and NPDR group (p = 0.234). Logistic regression showed that miR-9-3 hypermethylation increases the odds of presenting DR (OR: 2.826; p = 0.002) and PDR (OR: 5.472; p < 0.001). In addition, hypermethylation of miR-9-3 in the DR and NPDR subgroup was associated with higher serum VEGF-A levels (p = 0.012 and p = 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.

Keywords: Diabetic retinopathy; Epigenetic; Methylation; MicroRNAs; VEGF-A.

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