Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma

Purpose. To investigate systemic oxidative stress-induced DNA damage in patients with pseudoexfoliation glaucoma (PXG), we estimated plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a marker for oxidative DNA damage in comparison to controls. In addition, we also examined a combined effect o...

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Main Authors: Altaf A. Kondkar, Tahira Sultan, Taif A. Azad, Lubna Tabussum, Essam A. Osman, Saleh A. Al-Obeidan
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Ophthalmology
Online Access:http://dx.doi.org/10.1155/2019/8319563
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author Altaf A. Kondkar
Tahira Sultan
Taif A. Azad
Lubna Tabussum
Essam A. Osman
Saleh A. Al-Obeidan
author_facet Altaf A. Kondkar
Tahira Sultan
Taif A. Azad
Lubna Tabussum
Essam A. Osman
Saleh A. Al-Obeidan
author_sort Altaf A. Kondkar
collection DOAJ
description Purpose. To investigate systemic oxidative stress-induced DNA damage in patients with pseudoexfoliation glaucoma (PXG), we estimated plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a marker for oxidative DNA damage in comparison to controls. In addition, we also examined a combined effect of lysyl oxidase-like 1 (LOXL1) polymorphism status and 8-OHdG levels on PXG risk. Materials and Methods. A retrospective case-control study was performed to estimate plasma levels of 8-OHdG in 41 PXG patients and 45 nonglaucomatous controls using the enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicate on an automated ELISA analyzer. Two common polymorphisms (rs1048661 and rs3835942) in LOXL1 gene were genotyped by Sanger sequencing. Results. The mean and median levels of 8-OHdG were significantly increased in the PXG cases (p=0.032) and male subjects (p=0.041). Subjects with levels greater than the third quartile (75% percentile) exhibited a significant increased risk of PXG (odds ratio = 4.06, 95% confidence interval (CI = 1.11–14.80, p=0.029)). Within- and between-group comparisons showed that the mean levels were higher in individuals carrying the LOXL1 risk variant (G/G), but not statistically significant. In logistic regression analysis, both 8-OHdG (p=0.044) and rs3835942 (p=0.012) showed a statistically significant effect on the PXG outcome. However, the effect was lost when age, sex, and rs1048661 were included. A significant positive correlation was observed between 8-OHdG levels and intraocular pressure (R=0.284, p=0.008) and cup/disc ratio (R=0.233, p=0.031). Furthermore, in receiver operating characteristic analysis, the area under the curve was statistically significant (p=0.032) with a value of 0.635 (95% CI = 0.518–0.751). Conclusion. The study demonstrates an association of increased plasma levels of 8-OHdG in patients with PXG, supporting the role of oxidative stress, and increased oxidative DNA damage in PXG development.
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spelling doaj-art-a9be27f2b563460790eda44fb5020b0c2025-02-03T01:33:25ZengWileyJournal of Ophthalmology2090-004X2090-00582019-01-01201910.1155/2019/83195638319563Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation GlaucomaAltaf A. Kondkar0Tahira Sultan1Taif A. Azad2Lubna Tabussum3Essam A. Osman4Saleh A. Al-Obeidan5Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaAmbulatory Care, King Saud University, Riyadh, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaPurpose. To investigate systemic oxidative stress-induced DNA damage in patients with pseudoexfoliation glaucoma (PXG), we estimated plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a marker for oxidative DNA damage in comparison to controls. In addition, we also examined a combined effect of lysyl oxidase-like 1 (LOXL1) polymorphism status and 8-OHdG levels on PXG risk. Materials and Methods. A retrospective case-control study was performed to estimate plasma levels of 8-OHdG in 41 PXG patients and 45 nonglaucomatous controls using the enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicate on an automated ELISA analyzer. Two common polymorphisms (rs1048661 and rs3835942) in LOXL1 gene were genotyped by Sanger sequencing. Results. The mean and median levels of 8-OHdG were significantly increased in the PXG cases (p=0.032) and male subjects (p=0.041). Subjects with levels greater than the third quartile (75% percentile) exhibited a significant increased risk of PXG (odds ratio = 4.06, 95% confidence interval (CI = 1.11–14.80, p=0.029)). Within- and between-group comparisons showed that the mean levels were higher in individuals carrying the LOXL1 risk variant (G/G), but not statistically significant. In logistic regression analysis, both 8-OHdG (p=0.044) and rs3835942 (p=0.012) showed a statistically significant effect on the PXG outcome. However, the effect was lost when age, sex, and rs1048661 were included. A significant positive correlation was observed between 8-OHdG levels and intraocular pressure (R=0.284, p=0.008) and cup/disc ratio (R=0.233, p=0.031). Furthermore, in receiver operating characteristic analysis, the area under the curve was statistically significant (p=0.032) with a value of 0.635 (95% CI = 0.518–0.751). Conclusion. The study demonstrates an association of increased plasma levels of 8-OHdG in patients with PXG, supporting the role of oxidative stress, and increased oxidative DNA damage in PXG development.http://dx.doi.org/10.1155/2019/8319563
spellingShingle Altaf A. Kondkar
Tahira Sultan
Taif A. Azad
Lubna Tabussum
Essam A. Osman
Saleh A. Al-Obeidan
Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma
Journal of Ophthalmology
title Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma
title_full Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma
title_fullStr Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma
title_full_unstemmed Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma
title_short Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma
title_sort increased plasma levels of 8 hydroxy 2 deoxyguanosine 8 ohdg in patients with pseudoexfoliation glaucoma
url http://dx.doi.org/10.1155/2019/8319563
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