Association of Genetic Polymorphisms in Oxidative Stress and Inflammation Pathways with Glaucoma Risk and Phenotype.

Makedonka Atanasovska Velkovska,Tanja Blagus,Barbara Cvenkel,Katja Goričar,Vita Dolžan

doi:10.3390/jcm10051148

Makedonka Atanasovska Velkovska, Tanja Blagus + Show 3 more

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https://doi.org/10.3390/jcm10051148

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Abstract

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma.

Highlights

There is growing interest in the correlation between oxidative stress, inflammation, apoptosis and primary open-angle glaucoma (POAG) initiation and progression [1,2,3,4,5].Reactive oxygen species (ROS) are formed in the eyes, following a wide variety of stressors and are largely implicated in glaucoma pathogenesis
We evaluated the associations of selected single-nucleotide polymorphisms (SNPs) in antioxidative and inflammation pathways with the risk of glaucoma and the glaucoma phenotype
GPX1 rs1050450 polymorphism was mainly associated with the severity of POAG and with the phenotype such as the intraocular pressure (IOP) and C/D ratio

Summary

Introduction

There is growing interest in the correlation between oxidative stress, inflammation, apoptosis and primary open-angle glaucoma (POAG) initiation and progression [1,2,3,4,5].Reactive oxygen species (ROS) are formed in the eyes, following a wide variety of stressors and are largely implicated in glaucoma pathogenesis. In glaucoma, increased intraocular pressure (IOP), vascular dysregulation and immune system activation can trigger several changes in the retina and optic nerve, including disrupted axonal transport and neurofilament accumulation, microvascular abnormalities, extracellular matrix remodelling and glial cell activation. These alterations can lead to secondary damage such as excitotoxicity, neurotrophin deprivation, oxidative damage, mitochondrial dysfunction and, eventually, retinal ganglion cell death [5,14]. Neurodegeneration extends beyond the retina and optic nerve into the central nervous system [3,15]

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