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.

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.

Relationship of the Pro12Ala Polymorphism on the PPARy2 Gene With the Body Composition of Practitioners of Cyclic Exercises.

This study aimed to verify the association between the genotypic of the receptor gene activated by peroxisome proliferators gamma 2 (PPARy2) and the body composition and the specific indicators of adiposity in practitioners physical exercises, considering nutritional intake, age, and training load as influencing factors. It was conducted a cross-sectional study with 335 adults (47.9 ± 12.7 years, 138 men, body mass index/BMI = 27.0 ± 4.9 kg/m2), practitioners of aerobic exercises in cyclical modalities (running, walking and/or cycling, who spent 328.3 ± 193.6 kcal/day on physical training). The genotyping of the Pro12Ala polymorphism was performed using the PCR-RFLP technique and the body composition measured by bioimpedance (InBody 720). Energy expenditure was based on the compendium of physical activities and caloric intake was measured by 24 h recall questionnaire. The higher prevalence was for the Pro/Pro genotype (76.1% vs. 23.9% of Pro/Ala). Pro/Pro genotypic group showed significant higher mean values for body mass (BM) (p < 0.03 for men and p < 0.02 for women) and BMI (p < 0.00 for men and p < 0.02 for women) and %FAT (p < 0.00), waist-hip ratio (WHR) (p < 0.04), and visceral fat (VF) (p < 0.00) only in men compared to Pro/Ala. Higher frequency of Pro/Pro was observed in the category indicating BMI (p < 0.00 for men and p < 0.03 for women), WRH (p < 0.03 for men and p < 0.00 for women), and %FAT (p < 0.03) (in the latter case, only among men. It was also observed that the frequency of distribution of Pro/Ala in the eutrophic category of the BMI remained independent of all influencers, while WHR and %FAT were independent of the training load, but influenced by nutritional intake and age. In women, the frequency of Pro/Ala distribution at the lowest BMI and WHR values remained independent of all confounding variables. It is concluded that the Pro12Ala polymorphism in the PPARy2 gene consistently influences indicators of body composition and adiposity, regardless of the practitioners of physical training, but the relationship needs to be considered according to age and nutritional intake.