DNA Methylation Profiles of PSMA6 , PSMB5 , KEAP1 , and HIF1A Genes in Patients with Type 1 Diabetes and Diabetic Retinopathy.

We explored differences in the DNA methylation statuses of PSMA6 , PSMB5 , HIF1A , and KEAP1 gene promoter regions in patients with type 1 diabetes and different diabetic retinopathy (DR) stages. Study subjects included individuals with no DR (NDR, n = 41), those with non-proliferative DR (NPDR, n = 27), and individuals with proliferative DR or those who underwent laser photocoagulation (PDR/LPC, n = 46). DNA methylation was determined by Zymo OneStep qMethyl technique. The methylation of PSMA6 (NDR 5.9 (3.9-8.7) %, NPDR 4.5 (3.8-5.7) %, PDR/LPC 6.6 (4.7-10.7) %, p = 0.003) and PSMB5 (NDR 2.2 (1.9-3.7) %, NPDR 2.2 (1.9-3.0) %, PDR/LPC 3.2 (2.5-7.1) %, p < 0.01) differed across the groups. Consistent correlations were observed between the methylation levels of HIF1A and PSMA6 in all study groups. DNA methylation levels of PSMA6 , PSMB5 , and HIF1A genes were positively correlated with the duration of diabetes, HbA1c, and albuminuria in certain study groups. Univariate regression models revealed a significant association between the methylation level z-scores of PSMA6 , PSMB5 , and HIF1A and severe DR ( PSMA6 : OR = 1.96 (1.15; 3.33), p = 0.013; PSMB5 : OR = 1.90 (1.14; 3.16), p = 0.013; HIF1A : OR = 3.19 (1.26; 8.06), p = 0.014). PSMB5 remained significantly associated with DR in multivariate analysis. Our findings suggest significant associations between the severity of DR and the DNA methylation levels of the genes PSMA6 , PSMB5 , and HIF1A , but not KEAP1 gene.