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Gene polymorphism and plasma levels of miR-155 in diabetic retinopathy.

ABSTRACT: Circulating microRNA-155 (miR-155) is associated with type 2 diabetes mellitus (T2DM) and the rs767649 polymorphism in the pre-MIR155 gene is associated with miR-155 expression. However, their relationship with diabetic retinopathy (DR) is still unknown. Therefore, the aim of this case-control study was to test the hypothesis that the rs767649 polymorphism in the pre-MIR155 gene is associated with DR in South Brazilians with T2DM. We also evaluated the association of plasma levels of miR-155 with DR and the rs767649 polymorphism in a subgroup of subjects. The rs767649 polymorphism was genotyped in 139 blood donors and 546 T2DM patients (244 had no DR, 161 had non-proliferative DR and 141 had proliferative DR). miR-155 expression was quantified in 20 blood donors and 60 T2DM patients (20 from each group). Among T2DM patients, the carriership of the A allele and the A allele were more frequent in subjects with DR than in those without it (P < 0.05), and the A allele was independently associated with an increased risk of DR (adjusted OR = 2.12, 95% CI = 1.12-4.01). The plasma levels of miR-155 were lower in T2DM patients than in blood donors (P < 0.001). However, the miR-155 levels did not differ according to the presence and severity of DR or according to rs767649 genotypes among T2DM patients. These findings support that the rs767649 polymorphism in the pre-MIR155 gene is associated with DR in T2DM and that the miR-155 plasma levels might be associated with T2DM. Additional studies are needed to further investigate their clinical significance in DR and T2DM.

SUBMITTER: Polina ER

PROVIDER: S-EPMC6933831 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Gene polymorphism and plasma levels of miR-155 in diabetic retinopathy.

Polina E R ER Oliveira F M FM Sbruzzi R C RC Crispim D D Canani L H LH Santos K G KG

Endocrine connections 20191201 12

Circulating microRNA-155 (miR-155) is associated with type 2 diabetes mellitus (T2DM) and the rs767649 polymorphism in the pre-MIR155 gene is associated with miR-155 expression. However, their relationship with diabetic retinopathy (DR) is still unknown. Therefore, the aim of this case-control study was to test the hypothesis that the rs767649 polymorphism in the pre-MIR155 gene is associated with DR in South Brazilians with T2DM. We also evaluated the association of plasma levels of miR-155 wit ...[more]

PMID: 31751306

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Project description:BackgroundProliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic factors underlying PDR. This study aimed to investigate the plasma metabotype of patients with PDR and to identify novel metabolite markers for PDR. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of diabetic retinopathy.MethodsA total of 1024 patients with type 2 diabetes were screened. To match clinical parameters between case and control subjects, patients with PDR (PDR, n = 21) or those with a duration of diabetes of ≥10 years but without diabetic retinopathy (NDR, n = 21) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS).ResultsThe distinct metabolites between PDR and NDR groups were significantly enriched in 9 KEGG pathways (P < 0.05, impact > 0.1), namely, alanine, aspartate and glutamate metabolism, caffeine metabolism, beta-alanine metabolism, purine metabolism, cysteine and methionine metabolism, sulfur metabolism, sphingosine metabolism, and arginine and proline metabolism. A total of 63 altered metabolites played important roles in these pathways. Finally, 4 metabolites were selected as candidate biomarkers for PDR, namely, fumaric acid, uridine, acetic acid, and cytidine. The area under the curve for these biomarkers were 0.96, 0.95, 1.0, and 0.95, respectively.ConclusionsThis study suggested that impairment in the metabolism of pyrimidines, arginine and proline were identified as metabolic dysregulation associated with PDR. And fumaric acid, uridine, acetic acid, and cytidine might be potential biomarkers for PDR. Fumaric acid was firstly reported as a novel metabolite marker with no prior reports of association with diabetes or diabetic retinopathy, which might provide insights into potential new pathogenic pathways for diabetic retinopathy.

Dataset Information

Gene polymorphism and plasma levels of miR-155 in diabetic retinopathy.

Publications

Gene polymorphism and plasma levels of miR-155 in diabetic retinopathy.

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