The rs2442598 polymorphism in the ANGPT-2 gene is associated with risk for diabetic retinopathy in patients with type 1 diabetes mellitus in a Brazilian population

Abstract

Objective: As studies have reported the involvement of angiopoietin-2 (ANGPT-2) in the pathogenesis of diabetic retinopathy (DR), the aim of this study was to investigate the association between the ANGPT-2 rs2442598 polymorphism and DR. Materials and 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 the Hardy-Weinberg equilibrium. The frequency of the rs2442598 A allele was higher in cases compared to controls (p = 0.011). Moreover, the A/A genotype was more frequent in cases than in controls (p = 0.017) and was associated with risk for DR after adjustments for duration of DM, HbA1c, triglycerides, estimated glomerular filtration rate, and hypertension (odds ratio [OR] = 5.19, 95% confidence interval [CI] 1. 21-22.27). This association was maintained under recessive (OR = 4.78, 95% CI 1.14-19.99) and additive (OR = 6.861, 95% CI 1.45-32.38) inheritance models. Conclusion: Our data demonstrated, for the first time, an association between the ANGPT-2 rs2442598 A allele and risk for DR in T1DM patients from southern Brazil. Additional studies are necessary to replicate this association in other populations.

The brain–kidney–retinal axis in severe falciparum malaria

“…These findings are consistent with studies in patients with sepsis where an Angpt-2 gene variant (rs2920656C > T) associated with lower Angpt-2 protein levels was associated with a less severe sub-phenotypes of AKI [9]. Perturbations in the Angpt-Tie-2 pathway have been implicated in multiple forms of retinopathy [10,11] and polymorphisms in the ANGPT2 gene have also been implicated in retinopathy (rs2442598 G>A) [12]. Based on these findings, there is a strong reason to believe that malaria will impact choroidal thickness in children, as proposed by Burke et al, and studies should investigate the relationship between the Angpt-2-Tie-2 axis as it relates to the kidney, brain, and retina.…”

Beyond VEGF: Angiopoietin–Tie Signaling Pathway in Diabetic Retinopathy

“…The rs2442598A allele in the ANGPT-2 gene is associated with an increased risk for diabetic retinopathy in Brazilian patients with type 1 DM [165]. Intravitreal levels of Ang2 are also elevated in eyes with DME and PDR [166][167][168]. A recent systematic review and meta-analysis reported that intravitreal levels of Ang2 are elevated in eyes with PDR when compared to healthy non-diabetic eyes [169].…”

Factores de riesgo en retinopatía diabética, una perspectiva latinoamericana

“…) con RD, se encontró que tampoco hay una asociación de estos con RD 20 . Además, se analizaron polimorfismos del gen ANGPT-2 (SNP rs2442598); los autores encontraron que en pacientes con diabetes tipo 1 había una asociación entre el genotipo A/A y el alelo A con la susceptibilidad de padecer RD, y se encontraba con mayor frecuencia en pacientes que presentaban la complicación 21 . También, en diabetes tipo 1, se analizaron polimorfismos del gen ERBB3 (rs705708 alelo A) y su regulador PA2G4 (rs773120), que son polimorfismos que se han estudiado por su aparente relación con el riesgo para padecer diabetes tipo 1.…”