Glutathione <scp>S</scp>‐transferase omega‐2 polymorphism <scp><i>Asn142Asp</i></scp> modifies the risk of age‐related cataract in smokers and subjects exposed to ultraviolet irradiation

Stamenković, Miroslav; Radić, Tanja; Stefanović, Ivan; Ćorić, Vesna; Senćanić, Ivan; Plješa-Ercegovac, Marija; Matić, Marija; Jaksic, Vesna; Simić, Tatjana; Savić-Radojević, Ana

doi:10.1111/ceo.12180

Cited by 18 publications

(8 citation statements)

References 31 publications

(37 reference statements)

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“…Another DRG linked to cataract and oxidative stress is Gsto1 , which encodes a glutathione S-transferase (GST) omega 1 that is considered to function in oxidative stress response by mediating regeneration of ascorbate. Interestingly, homozygous GSTO1 Ala140Asp/ GSTO2 Asn142Asp haplotype carriers are associated with an elevated risk of cataracts in humans (Stamenkovic et al 2014). Gsto1 is identified as a direct target of Nrf2 in ChIP assays and is down-regulated in Mafg−/−:Mafk+/− mutant lens.…”

Section: Discussionmentioning

confidence: 99%

Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract

et al. 2015

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Although majority of the genes linked to early-onset cataract exhibit lens fiber cell-enriched expression, our understanding of gene regulation in these cells is limited to function of just eight transcription factors and largely in the context of crystallins. We report on small Maf transcription factors Mafg and Mafk as regulators of several non-crystallin human cataract-associated genes in fiber cells and establish their significance to this disease. We applied a bioinformatics tool for cataract gene discovery iSyTE to identify Mafg and its co-regulators in the lens, and generated various null-allelic combinations of Mafg:Mafk mouse mutants for phenotypic and molecular analysis. By age 4-months, Mafg−/−:Mafk+/− mutants exhibit lens defects that progressively develop into cataract. High-resolution phenotypic characterization of Mafg−/−:Mafk+/− mouse lens reveals severely disorganized fiber cells, while microarrays-based expression profiling identifies 97 differentially regulated genes (DRGs). Integrative analysis of Mafg−/−:Mafk+/− lens-DRGs with 1) binding-motifs and genomic targets of small Mafs and their regulatory partners, 2) iSyTE lens-expression data, and 3) interactions between DRGs in the String database, unravels a detailed small Maf regulatory network in the lens, several nodes of which are linked to cataract. This approach identifies 36 high-priority candidates from the original 97 DRGs. Significantly, 8/36 (22%) DRGs are associated with cataracts in human (GSTO1, MGST1, SC4MOL, UCHL1) or mouse (Aldh3a1, Crygf, Hspb1, Pcbd1), suggesting a multifactorial etiology that includes oxidative stress and mis-regulation of sterol synthesis. These data identify Mafg and Mafk as new cataract-associated candidates and define their function in regulating largely non-crystallin genes linked to human cataract.

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Section: Discussionmentioning

confidence: 99%

Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract

et al. 2015

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“…These enzymes catalyze the reaction of such compounds with the -SH group of glutathione, there by neutralizing their electrophilic sites and rendering the products more water soluble. Age related cataract is associated with a decline in the activity of GST in the lens (Stamenkovic et al, 2014). Reduced activity of GST in cataract was positively modulated by ECT treatment demonstrating the protective effect against oxidant attack.…”

Section: Groupsmentioning

confidence: 87%

Cassia tora leaves modulates selenite cataract by enhancing antioxidant status and preventing cytoskeletal protein loss in lenses of Sprague Dawley rat pups

Vasudevan

Abraham

2016

Journal of Ethnopharmacology

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“…The influence of GSTO2 polymorphism has also been investigated in the risk of hypothyroidism development and it has been reported that the carriers of variant GSTO2 genotype had almost five times higher risk for developing hypothyroidism (27). The study of Stamenkovic et al (29) addressed the influence of GSTO1 polymorphism Ala140Asp and GSTO2 polymorphism Asn142Asp on the risk of age-related cataract. The results indicate that mutant GSTO2*Asp genotype is associated with increased risk of age-related cataract in smokers and ultraviolet-exposed subjects.…”

Section: Discussionmentioning

confidence: 99%

“…An SNP of GSTO2 gene was found at nucleotide 424 causing an asparagine to aspartate substitution in amino acid 142 (N142D) of exon 4 (rs156697, 424 A to G) (23). Although the functional significance of GSTO1 and GSTO2 gene SNP is still under investigation, attempts were made to establish whether variant alleles confer higher risk of various types of malignancies (24, 25) and nonmalignant diseases (26–29). …”

Section: Introductionmentioning

confidence: 99%

Association of GSTO1 and GSTO2 Polymorphism with Risk of End-Stage Renal Disease Development and Patient Survival

Cimbaljevic¹,

Šuvakov

Matić

et al. 2016

Journal of Medical Biochemistry

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SummaryBackgroundOxidative stress in patients with end-stage renal disease (ESRD) is associated with long-term cardiovascular complications. The cytosolic family of glutathione S-transferases (GSTs) is involved in the detoxication of various toxic compounds and antioxidant protection. GST omega class members, GSTO1 and GSTO2 possess, unlike other GSTs, dehydroascorbate reductase and deglutathionylation activities. The aim of this study was to clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) as risk determinants for ESRD development, as well as in the survival of these patients.MethodsA total of 199 patients and 199 healthy subjects were included in the study and genotyped for both GSTO1 and GSTO2 polymorphism. Protein thiol and carbonyl groups as markers of protein oxidative damage were determined spectrophotometrically. Cox proportional hazard model and Kaplan-Meier analysis were performed to investigate the role of GSTO1 and GSTO2 genetic polymorphism on mortality of ESRD patients during the follow-up period (36 month).ResultsIndividuals carrying the variant GSTO2 GG genotype were at 2.45-fold higher risk of ESRD development compared to the wild type GSTO2 AA genotype (OR=2.45; 95%CI=1.18–5.07; p=0.016). The results of GSTO1/ GSTO2 haplotype analysis showed that the haplotype combination of GSTO1 (*A)/GSTO2 (*A) (GSTO1 variant/GSTO2 wild type allele) was protective for ESRD (OR=0.23 95%CI=0.12-0.44, p=0.001). Patients carrying at least one GSTO1 reference allele have shorter mean overall (Log rank=2.844, p =0.241) and cardiovascular survival probability (Log rank=4.211, p=0.122).ConclusionsGSTO polymorphisms have been shown to act as significant markers in assessing the risk of ESRD development and patients’ survival.

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Glutathione S‐transferase omega‐2 polymorphism Asn142Asp modifies the risk of age‐related cataract in smokers and subjects exposed to ultraviolet irradiation

Abstract: The results indicate that mutant GSTO2*Asp genotype is associated with increased risk of age-related cataract in smokers and ultraviolet-exposed subjects, suggesting a role of inefficient ascorbate regeneration in cataract development.

Cited by 18 publications

References 31 publications

Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract

Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract

Cassia tora leaves modulates selenite cataract by enhancing antioxidant status and preventing cytoskeletal protein loss in lenses of Sprague Dawley rat pups

Association of GSTO1 and GSTO2 Polymorphism with Risk of End-Stage Renal Disease Development and Patient Survival

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