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Background: Diabetic retinopathy (DR) is characterized by ischemia, hypoxia, and angiogenesis. Erythropoietin (EPO), an angiogenic hormone, is upregulated in DR, and the association of EPO genetic variants with DR is still uncertain, as conflicting results have been reported. Therefore, we performed a case-control study followed by a meta-analysis to investigate whether the rs1617640, rs507392, and rs551238 polymorphisms in EPO gene are associated with DR., Methods: The case-control study included 1042 Southern Brazilians with type 2 diabetes (488 without DR and 554 with DR). Eligible studies for the meta-analysis were searched from electronic databases up to June 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for five genetic inheritance models., Results: The minor alleles of the EPO polymorphisms had nearly the same frequency in all groups of patients (35%), and no association was detected with DR in the case-control study. The meta-analysis included 14 independent sets of cases and controls with 9117 subjects for the rs1617640 polymorphism and nine independent sets with more than 5000 subjects for the rs507392 and rs551238 polymorphisms. The G allele of the rs1617640 polymorphism was suggestively associated with DR under the dominant (OR = 0.82, 95% CI: 0.68-0.98), heterozygous additive (OR = 0.82, 95% CI: 0.69-0.97), and overdominant (OR = 0.88, 95% CI: 0.79-0.97) models. In the subgroup analyses, the G allele was also suggestively associated with proliferative DR (PDR), non-proliferative DR (NPDR), and DR (PDR + NPDR) among patients with type 1 diabetes (T1DM) or non-Asian ancestry. After considering the Bonferroni correction for multiple comparisons, the G allele remained associated with NPDR and DR in T1DM. Regarding the rs507392 and rs551238 polymorphisms, no association was found between these variants and DR., Conclusion: Our findings provide additional support to EPO as a susceptibility gene for DR, with the rs1617640 polymorphism deserving further investigation., (© 2022. The Author(s).)

MicroRNAs (miRNAs/miRs) are involved in the pathogenesis of diabetes mellitus and its chronic complications, and their circulating levels have emerged as potential biomarkers for the development and progression of diabetes. However, few studies have examined the expression of miRNAs in diabetic retinopathy (DR) in humans. This case-control study aimed to investigate whether the plasma levels of miR-29b and miR-200b are associated with DR in 186 South Brazilians with type 2 diabetes (91 without DR, 46 with non-proliferative DR and 49 with proliferative DR). We also included 20 healthy blood donors to determine the miRNA expression in the general population. Plasma levels of miR-29b and miR-200b were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferative DR was inversely associated with plasma levels of miR-29b (unadjusted OR = 0.694, 95% CI: 0.535-0.900, P = 0.006) and miR-200b (unadjusted OR = 0.797, 95% CI: 0.637-0.997, P = 0.047). However, these associations were lost after controlling for demographic and clinical covariates. In addition, patients with type 2 diabetes had lower miR-200b levels than blood donors. Our findings reinforce the importance of addressing the role of circulating miRNAs, including miR-29 and miR-200b, in DR., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aim: To investigate whether the -1082A > G polymorphism (rs1800896) in the interleukin-10 (IL10) gene is associated with diabetic retinopathy (DR) in Brazilians with type 2 diabetes mellitus., Methods: This case-control study included 847 outpatients with type 2 diabetes and 145 healthy blood donors. Four hundred and two patients had no DR, 253 had non-proliferative DR (NPDR), and 192 had proliferative DR (PDR). Genotyping was done by real-time PCR., Results: Genotype and allele frequencies were similar in patients and blood donors. In relation to the presence and severity of DR, the AA genotype was overrepresented among patients with NPDR, whereas the GG genotype was more frequent among patients with PDR. Multiple logistic regression analysis showed that the AA genotype was independently associated with increased risk of NPDR, after controlling for duration of diabetes, body mass index, and insulin use (adjusted OR = 1.50; 95% CI = 1.04-2.17). The GG genotype, however, did not remain associated with increased risk of PDR (adjusted OR = 1.49; 95% CI = 0.78-2.86)., Conclusions: This study identified, for the first time, an independent association of the -1082A > G polymorphism in the IL10 gene with NPDR in type 2 diabetes. This finding provides additional evidence supporting that genetic variants of IL10 are involved in the pathogenesis of DR., (Copyright © 2018 Elsevier B.V. All rights reserved.)