Dataset Information

The rs2442598 Polymorphism in ANGPT-2 Gene Is Associated With Risk for Diabetic Retinopathy in Patients With Type 1 Diabetes Mellitus From a Brazilian Population

ABSTRACT: Abstract Introduction: Angiopoietin-2 (ANGPT-2) is a member of a growth factor family that binds to the endothelial receptor tyrosine kinase 2 and regulates vascular development and function. Under hyperglycemic conditions, ANGPT-2 is upregulated and leads to vascular destabilization, pericyte dropout, and aggravation of inflammation. In this context, studies have reported the involvement of ANGPT-2 in the pathogenesis of diabetic retinopathy (DR). Thus, polymorphisms in ANGPT-2 gene may be of interest in this field. Objective: To investigate the association between the rs2442598 polymorphism in the ANGPT-2 gene and DR. Methods: This case-control study comprised 107 patients with type 1 diabetes mellitus (T1DM) and DR (cases) and 129 patients with T1DM without DR (controls) and with ≥10 years of DM. The ANGPT-2 rs2442598 (G/A) polymorphism was genotyped by real-time PCR using TaqMan MGB probes. Results: Genotype distributions of this polymorphism were consistent with Hardy-Weinberg Equilibrium. Frequency of the rs2442598 A allele was higher in cases compared to controls (P= 0.011). Moreover, the A/A genotype was higher in cases than controls (P= 0.017) and was associated with risk for DR after adjustment for duration of DM, HbA1c, triglycerides, estimated glomerular filtration rate, and presence of hypertension (OR= 5.19, IC95% 1.21 - 22.27). This association was maintained under the recessive (OR= 4.78, IC95% 1.14 - 19.99) and additive (OR= 6.861, IC95% 1.45 - 32.38) inheritance models. Conclusion: Our data demonstrate, for the first time, the association of the ANGPT-2 rs2442598 A allele with risk for DR in T1DM patients from Southern Brazil.

SUBMITTER: Dieter C

PROVIDER: S-EPMC8090649 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose:To assess the relationship between metformin use and the severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate the effect of metformin dosage on reducing the incidence of DR. Methods:The study population included patients with newly diagnosed T2DM, who were aged ?20 years and prescribed with antidiabetic drug therapy lasting ?90 days, as identified using the National Health Insurance Research Database between 2000 and 2012. We matched metformin users and nonusers by a propensity score. Cox proportional hazard regression analyses were used to compute and compare the risk of developing nonproliferative diabetic retinopathy (NPDR) in metformin users and nonusers. Results:Overall, 10,044 T2DM patients were enrolled. Metformin treatment was associated with a lower risk of NPDR (aHR 0.76, 95% CI 0.68-0.87) and sight-threatening diabetic retinopathy (STDR, aHR 0.29, 95% CI 0.19-0.45); however, the reduction in risk was borderline significant for STDR progression among NPDR patients (aHR 0.54, 95% CI 0.28-1.01). Combination therapy of metformin and DPP-4i exhibited a stronger but inverse relationship with NPDR development (aHR 0.32, 95% CI 0.25-0.41), especially at early (<3 months) stages of metformin prescription. These inverse relationships were also evident at different metformin doses and in adapted Diabetes Complications Severity Index scores (aDCSI). Moreover, combination therapy of metformin with sulfonylureas was associated with an increased risk of NPDR. Conclusion:Metformin treatment in patients with T2DM was associated with a reduced risk of NPDR, and a potential trend was found for a reduced STDR risk in patients who had previously been diagnosed with NPDR. Combining metformin with DPP-4i seemingly had a significantly beneficial effect against NPDR risk, particularly when aDCSI scores were low, and when metformin was prescribed early after T2DM diagnosis. These results may recommend metformin for early treatment of T2DM.

Dataset Information

The rs2442598 Polymorphism in ANGPT-2 Gene Is Associated With Risk for Diabetic Retinopathy in Patients With Type 1 Diabetes Mellitus From a Brazilian Population

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