Epigenetic Regulation of Sorbitol Dehydrogenase in Diabetic Retinopathy Patients: DNA Methylation, Histone Acetylation and microRNA-320

Ramzi Amin,1,* Hikmat Permana,2,* Arief Sjamsulaksan Kartasasmita,3,* Dany Hilmanto,4,* Rachmat Hidayat5,* 1Department of Ophthalmology, Faculty of Medicine, Universitas Sriwijaya, Palembang, Indonesia; 2Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; 3Department of Ophthalmology, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; 4Department of Pediatrics, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; 5Department of Medical Biology, Faculty of Medicine, Universitas Sriwijaya, Palembang, Indonesia*These authors contributed equally to this workCorrespondence: Ramzi Amin, Department of Ophthalmology, Faculty of Medicine, Universitas Sriwijaya, Jl Dr Moh Ali KM 3.5, Palembang, South Sumatera, 30126, Indonesia, Tel +62 882 2505 3819, Email [email protected]: This study aimed to investigate the correlation between epigenetic markers and sorbitol dehydrogenase (SDH) levels in patients with type 2 diabetes and diabetic retinopathy (DR).Patients and Methods: We conducted a case control study on 40 patients with type 2 diabetes and DR and 40 patients with type 2 diabetes without DR. Clinical data and ophthalmological examinations were performed to confirm the presence or absence of DR. Blood samples were collected for the analysis of DNA methylation, histone acetylation, microRNA-320 levels, and SDH enzyme activity. The epigenetic markers were evaluated using enzyme linked immunosorbent modified assay. The data were analyzed using statistical tests, including Spearman correlation and multiple linear regression.Results: In patients with DR, there was a significant negative correlation between microRNA-320 levels and SDH enzyme activity (r=− 0.968, p=0.000). No significant correlations were found between DNA methylation or histone acetylation and SDH activity. Multivariate analysis confirmed the strong negative correlation between microRNA-320 and SDH (r = − 0.727, p=0.000), with microRNA-320 explaining 58.1% of the variance in SDH levels.Conclusion: The findings suggest that microRNA-320 plays a crucial role in regulating SDH enzyme activity in patients with type 2 diabetes and DR. The development of microRNA-320-based therapies, such as miRNA mimics or antagomirs, may offer a novel approach to modulating SDH activity and mitigating the detrimental effects of the polyol pathway in DR. Further researches are needed to validate the results and mechanism underlying the correlation between epigenetic regulation SDH in DR.Keywords: case control studies, genetic, linear models, microRNAs, type 2 diabetes mellitus