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 (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.

MTHFR Polymorphisms and Cardiac Parameters in Patients with Diabetic Retinopathy.

BACKGROUND: Diabetes Mellitus (DM) is directly associated with cardiovascular dysfunctions and microvascular complications, such as diabetic retinopathy (DR). The association between DR and increased risks of developing cardiovascular diseases has been described. The low activity of the Methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the metabolism of homocysteine, can lead to hyperhomocysteinemia that has already been related to cardiac outcomes and resistance to insulin. The A1298C and C677T polymorphisms in the MTHFR can reduce enzyme activity. OBJECTIVE: The study aims to analyze the association between MTHFR genotypes and cardiac parameters in patients with DR. METHODS: DM patients diagnosed with DR (n=65) were categorized and compared according to MTHFR genotypes A1298C (AA and AC+CC groups) and C677T (CC and CT+TT) groups; biochemical, cardiological, anthropometric, genetic, lifestyle and vitamin B9 and B12 consumption variables. Fischer's exact test and Poisson regression were performed to assess the relationship between variables. RESULTS: Comparing echocardiographic and electrocardiogram parameters within genotypic groups, we found a significant association between left atrial dilation and C677T polymorphism. Left atrium diameter was higher in the T allele carriers (CT+TT group), with a prevalence ratio of 0.912. This association was confirmed in the regression model, including confounding variables. The other cardiac structural and functional parameters studied were not significantly associated with the A1298C or C677T genotypes. CONCLUSION: The MTHFR C677T genotype may contribute to atrial remodeling in RD patients. We found an association between the diameter of the left atrium and the T allele of the MTHFR C677T polymorphism in patients with DR.

Metabolic impact of the VDR rs1544410 in diabetic retinopathy.

AIMS: To investigate the association between BsmI and DM2 in patients with and without DR and to correlate with clinical parameters in a population in northeastern Brazil. METHODS: Cross-sectional case-control study in which data were collected from 285 individuals, including 128 patients with DM2 and 157 with DR. Clinical, biochemical and anthropometric parameters were analyzed, in addition to the single nucleotide polymorphism (SNP) BsmI of the VDR gene (rs1544410), genotyped by PCR-RFLP. RESULTS: In the DR group we found a greater number of patients using insulin therapy (p = 0.000) and with longer duration of DM2 (p = 0.000), in addition to higher serum creatinine values (p = 0.001). Higher fasting glucose levels and higher frequency of insulinoterapy were independently observed in patients with DR and b allele carriers, when compared to BB. CONCLUSION: The association of the bb/Bb genotypes (rs1544410) of the VDR gene with increased blood glucose levels and insulinoterapy may represent worse glicemic control in rs1544410 b allele carriers in DR Latin American individuals.

Methylation Profile of miR-9-1 and miR-9-1/-9-3 as Potential Biomarkers of Diabetic Retinopathy.

AIMS: Analysis of the relationship between the methylation profile of miR-9-1 or miRs -9-1 / -9-3 and diabetic retinopathy. BACKGROUND: Diabetic Retinopathy (DR) is a frequent complication of Diabetes mellitus and it has a decisive impact on the quality of life, as it is one of the biggest causes of blindness in the adult population. Levels of microRNA-9 have been shown to be related to diabetes but little is known about its involvement with DR in humans. OBJECTIVE: To analyze the relationship between the methylation profile of miR-9-1 or miRs -9-1/-9-3 and DR. METHODS: 103 patients diagnosed with diabetes for 5 to 10 years were analyzed. The data were categorized according to clinical, biochemical, lifestyle and anthropometric parameters. DNA extracted from leukocyte samples was used to determine the methylation profile of miRs-9-1 and -9-3 using a specific methylation PCR assay. RESULTS: miR-9-1 methylation was related to diabetic retinopathy, indicating that methylation of this miR increases the chances of presenting retinopathy up to 5 times. In our analyses, diabetics with lower levels of creatinine and CRP showed significant reductions (99% and 97%) in presenting DR. Methylation of both miRs-9-1 and 9-3 methylated increases the chances of presenting DR by 8 times; in addition, a sedentary lifestyle can increase the risk for the same complication by up to 6 times. CONCLUSION: Our results suggest that both methylation of miR-9-1 and e miRs-9-1 / 9-3 favors DR in patients with diabetes in a period of 5 to 10 years of diagnosis.

Hypermethylation in the promoter of the MTHFR gene is associated with diabetic complications and biochemical indicators.

BACKGROUND: DNA methylation is an epigenetic mechanism for regulating the transcription of many genes and has been linked to the development of various diseases. A promising gene to investigate is methylenetetrahydrofolate reductase (MTHFR), since the enzyme methylenetetrahydrofolate reductase (MTHFR) promotes methyl radical synthesis in the homocysteine cycle and can provide methyl groups for DNA methylation. In addition, several studies have correlated gene polymorphisms of this enzyme with a greater risk of diabetes, but little is known regarding the relationship between epigenetic changes in this gene and diabetes and its complications. The aim of this study was to investigate the relationship between methylation profile in the MTHFR gene promoter and biochemical, inflammatory and oxidative stress markers in individuals with type 2 diabetes (T2DM) who have been diagnosed for 5-10 years with or without diabetic retinopathy (DR) and nephropathy (DN). METHODS: Specific PCR for methylation (MSP) was used to analyze MTHFR methylation profile in leucocytes DNA. Biochemical markers (glycemia, glycated hemoglobin, total cholesterol, LDL, HDL, triglycerides, serum creatinine), inflammatory markers (C-reactive protein and alpha-1 acid glycoprotein) and oxidative stress (total antioxidant and malonaldehyde) were determined in peripheric blood samples and microalbuminuria in 24 h urine samples. The X2 and Mann-Whitney statistical tests were performed and p < 0.05 were considered significant. RESULTS: The hypermethylated profile was most frequently observed in individuals with retinopathy (p < 0.01) and was associated with higher total cholesterol and LDL levels (p = 0.0046, 0.0267, respectively). Individuals with DN and hypermethylated profiles had higher levels of alpha-1 acid glycoprotein (p = 0.0080) and total antioxidant capacity (p = 0.0169) compared to subjects without complications. CONCLUSIONS: Hypermethylation in the promoter of the MTHFR gene is associated with the occurrence of DR and with biochemical, inflammatory and oxidative stress parameters in the context of chronic complications.