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Mostafa Saadat - One of the best experts on this subject based on the ideXlab platform.
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Minireview: ARSENIC, GSTO2 ASN142ASP POLYMORPHISM, HEALTH AND TREATMENT
2016Co-Authors: Mohammad Masoudi, Mostafa SaadatAbstract:Arsenic is a natural metallic element found in low concentrations in virtually every part of the environment, including waters and foods. The ingestion of arsenic by humans can cause a variety of disorders. Glutathione S-transferase omega (GSTO) is a member of phase II xeno-biotic metabolizing enzymes. GSTO2 (a member of GST omega) participates in detoxifica-tion of inorganic arsenic. In human, the A>G transition at nucleotide position 424 of GSTO2 was reported. This variation causes an Asn142Asp substitution. The Asp142 allozyme was expressed at approximately 80 % of the level of Asn142 allozyme. It is hypothesized that the GSTO2 polymorphism may alter the risk of several diseases which are related to chronic arse-nic poisoning. On the other hand, because arsenic trioxide is used for treatment of acute pro-myelocytic leukemia; it is possible that Asn142 allozyme may decrease the therapeutic ef-fect(s) of the drug
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Influence of GSTO2 (N142D) genetic polymorphism on acute renal rejection
Molecular Biology Reports, 2013Co-Authors: Nioosha Nekooie-marnany, Iraj Saadat, Mohammad-hossein Karimi, Jamshid Roozbeh, Mostafa SaadatAbstract:Acute renal allograft rejection remains an important problem following kidney transplantation. Several immunological and non-immunological factors intervene in renal graft rejection. Glutathione S -transferase super family is one of the important enzymes for biotransformation of both exogenous and endogenous xenobiotic compounds such as immunosuppressive drugs. The new class of this family is omega that includes two subunits GSTO1 and GSTO2 . In this study 282 samples were collected from renal recipients of Namazi hospital in Shiraz-Iran during 2007–2010 years. Also 300 healthy samples as control group were collected from Shiraz population, included in our study. The primary outcome of this study was defined as biopsy-proven acute rejection during 1 year of renal transplantation. We applied polymerase chain reaction–restriction fragment length polymorphism method for determination of GSTO2 N142D polymorphism. Our result showed no significant association between GSTO2 polymorphism and acute rejection. Also this genetic variant has no significant effect with the risk of end stage renal disease. Cadaveric donor type for acute rejection significantly differed between acute rejection and non acute rejection patients ( P = 0.004). The combination effect of donor type and GSTO2 polymorphism indicates DD genotype with cadaver donor type increase risk of acute rejection (OR = 3.82, 95 % CI 1.80–12.37, P = 0.02).
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Genetic polymorphism of N142D GSTO2 and susceptibility to breast cancer: a meta-analysis
Molecular Biology Research Communications, 2012Co-Authors: Mostafa SaadatAbstract:A B S T R A C T To establish a comprehensive picture of the relationship between glutathione S -transferase omega 2 (GSTO2; MIM: 612314) gene N142D variant (rs. 156697) and breast cancer risk, the present meta-analysis was carried out. Studies published up to July 2012 with information about GSTO2 polymorphism and breast cancer risk were identified using several electronic databases. We identified 4 eligible studies, including 2678 subjects (1316 patients, and 1362 healthy controls) in relation to the N142D polymorphism of GSTO2 and risk of breast cancer. There was no heterogeneity between studies. Considering all of the studies, the DD (OR=1.29, 95%CI: 0.991.67, P=0.055) and ND (OR=1.03, 95%CI: 0.88-1.21, P=0.697) genotypes, did not alter the risk of breast cancer in comparison with the NN genotype. Therefore, it is suggested that if the number of studies increased, finding a significant association between N142D polymorphism of GSTO2 and susceptibility to breast cancer would be very probable .
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Association between cataract and genetic polymorphisms of GSTM1, GSTT1, and GSTO2 with respect of work place.
Molecular vision, 2012Co-Authors: Iraj Saadat, Zainab Ahmadi, Majid Farvardin-jahromi, Mostafa SaadatAbstract:PURPOSE To investigate whether genetic polymorphisms of glutathione S-transferases (GSTM1, GSTT1, and GSTO2) in relation to the work place contribute to the development of cataract. METHODS The present case-control study consisted of 186 patients (108 females, 78 males) with cataract and 195 gender-matched healthy controls (111 females, 84 males) were randomly selected from unrelated volunteers in the same clinic. The GSTM1, GSTT1, and GSTO2 genotypes were determined using polymerase chain reaction (PCR) based methods. RESULTS The null genotype of GSTM1 increased the risk of cataract (OR=1.51, 95%CI: 1.01-2.26, p=0.045). The prevalence of GSTT1 and GSTO2 genotypes was similar between cases and controls. There was significant difference between cases and controls for work place (χ(2)=4.16, df=1, p=0.041). Genetic polymorphisms (GSTM1, GSTO2) and work place that were significant by p
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association between cataract and genetic polymorphisms of gstm1 gstt1 and GSTO2 with respect of work place
Molecular Vision, 2012Co-Authors: Iraj Saadat, Zainab Ahmadi, Majid Farvardinjahromi, Mostafa SaadatAbstract:PURPOSE To investigate whether genetic polymorphisms of glutathione S-transferases (GSTM1, GSTT1, and GSTO2) in relation to the work place contribute to the development of cataract. METHODS The present case-control study consisted of 186 patients (108 females, 78 males) with cataract and 195 gender-matched healthy controls (111 females, 84 males) were randomly selected from unrelated volunteers in the same clinic. The GSTM1, GSTT1, and GSTO2 genotypes were determined using polymerase chain reaction (PCR) based methods. RESULTS The null genotype of GSTM1 increased the risk of cataract (OR=1.51, 95%CI: 1.01-2.26, p=0.045). The prevalence of GSTT1 and GSTO2 genotypes was similar between cases and controls. There was significant difference between cases and controls for work place (χ(2)=4.16, df=1, p=0.041). Genetic polymorphisms (GSTM1, GSTO2) and work place that were significant by p<0.3 in the univariate analysis were included in the analysis for investigating the additive effects of the genotypes and work place on risk of cataract. Statistical analysis showed that the risk of cataract increased as a function of number of putative high risk factors (χ(2)=8.001, p=0.005). CONCLUSIONS This finding suggests that the polymorphisms of GSTM1 and GSTO2 and also work place may act additively for developing cataract.
Hung Yi Chiou - One of the best experts on this subject based on the ideXlab platform.
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Genetic polymorphisms in glutathione S-transferase (GST) superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan
Journal of biomedical science, 2011Co-Authors: Ling I. Hsu, Yu Mei Hsueh, Yuan Hung Wang, Wu Ping Chen, Tse Yen Yang, Yu Hsin Chen, Ya Tang Liao, Hung Yi ChiouAbstract:Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC) is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers. To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped. The GSTT1 null was marginally associated with increased urothelial carcinoma (UC) risk (HR, 1.91, 95% CI, 1.00-3.65), while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE) ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80). The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, p = 0.0151) and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22). The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20). Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183)A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74) when compared to the all-wildtype reference, respectively. The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.
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Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes.
Environmental research, 2011Co-Authors: Yi-chen Hsieh, Li-ming Lien, Wen Ting Chung, Fang-i Hsieh, Pei Fan Hsieh, Hung Pin Tseng, Hung Yi Chiou, Chien-jen ChenAbstract:Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50μg/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50μg/l).
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Abstract 4694: Genetic variants ofGSTO1, GSTO2, SULT1A1andALDH2, environmental exposures and risk of urothelial cancer in Taiwan
Epidemiology, 2010Co-Authors: Yuan Hung Wang, Kun Hung Shen, Guang Dar Juang, Shauh Der Yeh, Cheng-hung Shen, Hung Yi ChiouAbstract:Introduction: Cigarette smoking, arsenic and occupational exposures are known risk factors of urothelial cancer (UC). Some studies also found that alcohol consumption may be associated with bladder cancer. Phase II enzymes including Glutathione S- transferases (GSTs) or Sulfotransferase (SULT) are responsible to metabolize these environmental carcinogens as well as aldehyde dehydrogenase (ALDH) is an alcohol- metabolized enzyme. To investigate the gene-gene and gene-environment interactions on UC risk, this study included environmental exposures of cigarette smoking, alcohol consumption, arsenic and risk-occupations, and genetic variants of GSTO1, GSTO2, SULT1A1 and ALDH2 in combined analyses. Materials and Methods: A total of 540 pathologically-confirmed UC cases and 540 cancer-free controls, frequency-matched on age, were recruited from individuals who admitted to the same hospitals with UC cases for a health examination. Genetic variants of these enzymes were determined by PCR-RFLP method. A goodness-of-fit X 2 test was performed to examine Hardy-Weinberg Equilibrium (HWE). We used an unconditional multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype analysis was calculated by Haploview 3.2. Results: Cigarette smoking, arsenic and risk occupational exposures are significantly associated with UC risk. Study subjects with both of cigarette smoking and alcohol consumption have a significantly higher UC risk of 3.0. Significantly increased UC risks of 1.6, 2.5 and 1.8 were found for those carrying GSTO2 A424G-G/G, GSTO2 A-183G -G/G and SULT1A1 G638A-G/G genotypes, respectively. Individuals with risk diplotypes of GSTO1/2 also have a significantly higher UC risk of 1.8. Those carrying one or more risk genotypes/diplotypes of these enzymes have a significantly increased UC risk (OR=2.3). Subjects with cigarette smoking/alcohol consumption and occupational exposures (≥1), arsenic exposure (high), and risk genotypes/ diplotypes of these enzymes (≥1) have a significantly increased UC risk of 6.8. Conclusion: In addition to significant effects from exposures of environmental risk factors and risk genotypes/diplotypes of these enzymes on UC risk, the effects on the development of UC will be more predominant especially under the existence of gene-environment interactions. Therefore, a larger sample size and other functional polymorphisms of candidate genes should be took into consideration to provide a more comprehensive understanding of UC. Keywords: Glutathione S- transferases; Sulfotransferase; Aldehyde dehydrogenase; Urothelial cancer Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4694.
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a significantly joint effect between arsenic and occupational exposures and risk genotypes diplotypes of cyp2e1 gsto1 and GSTO2 on risk of urothelial carcinoma
Toxicology and Applied Pharmacology, 2009Co-Authors: Yuan Hung Wang, Hung Yi Chiou, Chien-jen Chen, Kun Hung Shen, Cheng Huang Shen, Guang Dar Juang, Ling I. Hsu, Shauh Der YehAbstract:Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR]=2.9; 95% confidence interval [CI]=1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.
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A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma.
Toxicology and applied pharmacology, 2009Co-Authors: Yuan Hung Wang, Hung Yi Chiou, Shauh Der Yeh, Kun Hung Shen, Cheng Huang Shen, Guang Dar Juang, Ling I. Hsu, Chien-jen ChenAbstract:Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR]=2.9; 95% confidence interval [CI]=1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.
Philip G. Board - One of the best experts on this subject based on the ideXlab platform.
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Structure, function and disease relevance of Omega-class glutathione transferases
Archives of Toxicology, 2016Co-Authors: Philip G. Board, Deepthi MenonAbstract:The Omega-class cytosolic glutathione transferases (GSTs) have distinct structural and functional attributes that allow them to perform novel roles unrelated to the functions of other GSTs. Mammalian GSTO1-1 has been found to play a previously unappreciated role in the glutathionylation cycle that is emerging as significant mechanism regulating protein function. GSTO1-1-catalyzed glutathionylation or deglutathionylation of a key signaling protein may explain the requirement for catalytically active GSTO1-1 in LPS-stimulated pro-inflammatory signaling through the TLR4 receptor. The observation that ML175 a specific GSTO1-1 inhibitor can block LPS-stimulated inflammatory signaling has opened a new avenue for the development of novel anti-inflammatory drugs that could be useful in the treatment of toxic shock and other inflammatory disorders. The role of GSTO2-2 remains unclear. As a dehydroascorbate reductase, it could contribute to the maintenance of cellular redox balance and it is interesting to note that the GSTO2 N142D polymorphism has been associated with multiple diseases including Alzheimer’s disease, Parkinson’s disease, familial amyotrophic lateral sclerosis, chronic obstructive pulmonary disease, age-related cataract and breast cancer.
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structural insights into the dehydroascorbate reductase activity of human omega class glutathione transferases
Journal of Molecular Biology, 2012Co-Authors: Huina Zhou, Philip G. Board, Joseph Brock, Aaron J OakleyAbstract:Abstract The reduction of dehydroascorbate (DHA) to ascorbic acid (AA) is a vital cellular function. The omega-class glutathione transferases (GSTs) catalyze several reductive reactions in cellular biochemistry, including DHA reduction. In humans, two isozymes (GSTO1-1 and GSTO2-2) with significant DHA reductase (DHAR) activity are found, sharing 64% sequence identity. While the activity of GSTO2-2 is higher, it is significantly more unstable in vitro . We report the first crystal structures of human GSTO2-2, stabilized through site-directed mutagenesis and determined at 1.9 A resolution in the presence and absence of glutathione (GSH). The structure of a human GSTO1-1 has been determined at 1.7 A resolution in complex with the reaction product AA, which unexpectedly binds in the G-site, where the glutamyl moiety of GSH binds. The structure suggests a similar mode of ascorbate binding in GSTO2-2. This is the first time that a non-GSH-based reaction product has been observed in the G-site of any GST. AA stacks against a conserved aromatic residue, F34 (equivalent to Y34 in GSTO2-2). Mutation of Y34 to alanine in GSTO2-2 eliminates DHAR activity. From these structures and other biochemical data, we propose a mechanism of substrate binding and catalysis of DHAR activity.
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S-(4-Nitrophenacyl)glutathione is a specific substrate for glutathione transferase omega 1-1.
Analytical biochemistry, 2007Co-Authors: Philip G. Board, Marjorie Coggan, Huina Zhou, Aaron J Oakley, Jean Cappello, Marion W. AndersAbstract:Glutathione transferase omega 1-1 (GSTO1-1) catalyzes the biotransformation of arsenic and is implicated as a factor influencing the age-at-onset of Alzheimer’s disease and the posttranslational activation of interleukin 1β (IL-1β). Investigation of the biological role of GSTO1-1 variants has been hampered by the lack of a specific assay for GSTO1-1 activity in tissue samples that contain other GSTs and other enzymes with similar catalytic specificities. Previous studies (P. G. Board and M. W. Anders, Chem. Res. Toxicol. 20 (2007) 149–154) have shown that GSTO1-1 catalyzes the reduction of S-(phenacyl)glutathiones to acetophenones. A new substrate, S-(4-nitrophenacyl)glutathione (4NPG), has been prepared and found to have a high turnover with GSTO1-1 but negligible activity with GSTO2-2 and other members of the glutathione transferase superfamily. A spectrophotometric assay with 4NPG as a substrate has been used to determine GSTO1-1 activity in several human breast cancer cell lines and in mouse liver and brain tissues.
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Glutathione Transferase Omega 1 Catalyzes the Reduction of S-(Phenacyl)glutathiones to Acetophenones
Chemical research in toxicology, 2007Co-Authors: Philip G. Board, M. W. AndersAbstract:S-(Phenacyl)glutathione reductase (SPG-R) plays a significant role in the biotransformation of reactive α-haloketones to nontoxic acetophenones. Comparison of the apparent subunit size, amino acid composition, and catalysis of the reduction of S-(phenacyl)glutathiones indicated that a previously described rat SPG-R (Kitada, M., McLenithan, J. C., and Anders, M. W. (1985) J. Biol. Chem. 260, 11749−11754) is homologous to the omega-class glutathione transferase GSTO1-1. The available data show that the SPG-R reaction is catalyzed by GSTO1-1 and not by other GSTs, including the closely related GSTO2-2 isoenzyme. In the proposed reaction mechanism, the active-site cysteine residue of GSTO1-1 reacts with the S-(phenacyl)glutathione substrate to give an acetophenone and a mixed disulfide with the active-site cysteine; a second thiol substrate (e.g., glutathione or 2-mercaptoethanol) reacts with the active-site disulfide to regenerate the catalytically active enzyme and to form a mixed disulfide. A new spectroph...
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characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of omega class glutathione transferase variants implications for arsenic metabolism and the age at onset of alzheimer s and parkinson s diseases
Pharmacogenetics and Genomics, 2005Co-Authors: Erica Schmuck, Astrid K Whitbread, N Tetlow, Anneke C. Blackburn, Philip G. Board, Juleen A. Cavanaugh, Amir MasoumiAbstract:There are two functional Omega class glutathione transferase (GST) genes in humans. GSTO1 is polymorphic with several coding region alleles, including an A140D substitution, a potential deletion of E155 and an E208K substitution. GSTO2 is also polymorphic with an N142D substitution in the coding reg
Iraj Saadat - One of the best experts on this subject based on the ideXlab platform.
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Association of GSTO2 (N142D) Genetic Polymorphism and Acute Rejection of Liver.
International journal of organ transplantation medicine, 2016Co-Authors: Mohammad Bagher Khosravi, Iraj Saadat, Mohammad-hossein KarimiAbstract:Background: Acute rejection is the main problem in liver transplantation that occurs in the first days or months of transplantation. It includes histological and cellular rejection. Acute histological rejection is confirmed by biopsy. Glutathione S-transferase family is the most important genes in phase II detoxification working in xenobiotic and drug metabolism. GSTO2 is one of the members of this family. GSTO2 (N142D) polymorphism may influence metabolism of immunosuppressive drugs. Objective: To determine if GSTO2 polymorphism has association with acute liver rejection. Methods: The present study included 120 patients with histological-proven acute liver rejection and 182 patients without acute rejection. Both groups were matched for sex and age. To determine variants of GSTO2 , we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There was a significant association between the GSTO2 genotype and acute liver rejection (NN: OR: 3.642, 95% CI: 1.179–5.444) and (ND: OR: 2.533, 95% CI: 1.672–8.149) compared to those with DD geneotype. Conclusion: Recipients with either NN or ND genotype for GSTO2 are more likely to develop acute liver rejection compared to those with DD genotype.
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Influence of GSTO2 (N142D) genetic polymorphism on acute renal rejection
Molecular Biology Reports, 2013Co-Authors: Nioosha Nekooie-marnany, Iraj Saadat, Mohammad-hossein Karimi, Jamshid Roozbeh, Mostafa SaadatAbstract:Acute renal allograft rejection remains an important problem following kidney transplantation. Several immunological and non-immunological factors intervene in renal graft rejection. Glutathione S -transferase super family is one of the important enzymes for biotransformation of both exogenous and endogenous xenobiotic compounds such as immunosuppressive drugs. The new class of this family is omega that includes two subunits GSTO1 and GSTO2 . In this study 282 samples were collected from renal recipients of Namazi hospital in Shiraz-Iran during 2007–2010 years. Also 300 healthy samples as control group were collected from Shiraz population, included in our study. The primary outcome of this study was defined as biopsy-proven acute rejection during 1 year of renal transplantation. We applied polymerase chain reaction–restriction fragment length polymorphism method for determination of GSTO2 N142D polymorphism. Our result showed no significant association between GSTO2 polymorphism and acute rejection. Also this genetic variant has no significant effect with the risk of end stage renal disease. Cadaveric donor type for acute rejection significantly differed between acute rejection and non acute rejection patients ( P = 0.004). The combination effect of donor type and GSTO2 polymorphism indicates DD genotype with cadaver donor type increase risk of acute rejection (OR = 3.82, 95 % CI 1.80–12.37, P = 0.02).
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Association between cataract and genetic polymorphisms of GSTM1, GSTT1, and GSTO2 with respect of work place.
Molecular vision, 2012Co-Authors: Iraj Saadat, Zainab Ahmadi, Majid Farvardin-jahromi, Mostafa SaadatAbstract:PURPOSE To investigate whether genetic polymorphisms of glutathione S-transferases (GSTM1, GSTT1, and GSTO2) in relation to the work place contribute to the development of cataract. METHODS The present case-control study consisted of 186 patients (108 females, 78 males) with cataract and 195 gender-matched healthy controls (111 females, 84 males) were randomly selected from unrelated volunteers in the same clinic. The GSTM1, GSTT1, and GSTO2 genotypes were determined using polymerase chain reaction (PCR) based methods. RESULTS The null genotype of GSTM1 increased the risk of cataract (OR=1.51, 95%CI: 1.01-2.26, p=0.045). The prevalence of GSTT1 and GSTO2 genotypes was similar between cases and controls. There was significant difference between cases and controls for work place (χ(2)=4.16, df=1, p=0.041). Genetic polymorphisms (GSTM1, GSTO2) and work place that were significant by p
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association between cataract and genetic polymorphisms of gstm1 gstt1 and GSTO2 with respect of work place
Molecular Vision, 2012Co-Authors: Iraj Saadat, Zainab Ahmadi, Majid Farvardinjahromi, Mostafa SaadatAbstract:PURPOSE To investigate whether genetic polymorphisms of glutathione S-transferases (GSTM1, GSTT1, and GSTO2) in relation to the work place contribute to the development of cataract. METHODS The present case-control study consisted of 186 patients (108 females, 78 males) with cataract and 195 gender-matched healthy controls (111 females, 84 males) were randomly selected from unrelated volunteers in the same clinic. The GSTM1, GSTT1, and GSTO2 genotypes were determined using polymerase chain reaction (PCR) based methods. RESULTS The null genotype of GSTM1 increased the risk of cataract (OR=1.51, 95%CI: 1.01-2.26, p=0.045). The prevalence of GSTT1 and GSTO2 genotypes was similar between cases and controls. There was significant difference between cases and controls for work place (χ(2)=4.16, df=1, p=0.041). Genetic polymorphisms (GSTM1, GSTO2) and work place that were significant by p<0.3 in the univariate analysis were included in the analysis for investigating the additive effects of the genotypes and work place on risk of cataract. Statistical analysis showed that the risk of cataract increased as a function of number of putative high risk factors (χ(2)=8.001, p=0.005). CONCLUSIONS This finding suggests that the polymorphisms of GSTM1 and GSTO2 and also work place may act additively for developing cataract.
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Association between N142D genetic polymorphism of GSTO2 and susceptibility to colorectal cancer
Molecular Biology Reports, 2011Co-Authors: Mohammad Masoudi, Iraj Saadat, Shahpour Omidvari, Mostafa SaadatAbstract:Expression pattern analysis has been revealed that glutathione S -transferase omega 2 (GSTO2, a member of class omega) is ubiquitously expressed. Over expression of GSTO2 induced apoptosis. The gene encoding GSTO2 was localized to human chromosome 10q24.3, a region that may harbor gene(s) involved in the developing of colorectal cancer. To investigate the association between GSTO2 N142D genetic polymorphism and susceptibility to colorectal cancer the present study was done. We studied 63 (26 females, 37 males) colorectal cancer patients and 126 (52 females, 74 males) healthy individuals. The control subjects were frequency matched for age and gender with the colorectal cancer group. The genotypes were performed using RFLP-PCR method. The ND and DD genotypes were not associated with risk of colorectal cancer, in comparison with the NN genotype. Family history for cancer in the first degree of relatives significantly differed between cases and controls ( P = 0.012). The profiles of GSTO2 genotypes and family history in control and cancerous groups were compared to each other. Subjects with NN genotype and positive family history significantly were at high risk to develop colorectal cancer in comparison with subjects with DD or ND genotypes and negative family history ( P = 0.003). Present findings indicating that GSTO2 NN genotype increase the risk of colorectal cancer in persons with positive family history for cancer in the first degree relatives.
Dejan Dragicevic - One of the best experts on this subject based on the ideXlab platform.
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GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients.
Cancers, 2019Co-Authors: Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Dejan Dragicevic, Marija Matic, Tatjana Djukic, Zoran Bukumiric, Nataša Avramović, Smiljana Mihailovic, Zoran DzamicAbstract:Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis.
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Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma.
The Tohoku journal of experimental medicine, 2018Co-Authors: Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Gordana Basta-jovanovic, Sanja Radojevic-skodric, Dejan Dragicevic, Marija Matic, Ljiljana Bogdanovic, Zoran Dzamic, Tatjana SimicAbstract:Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5' untranslated (5'UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype], suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5'UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.
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GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder
International Urology and Nephrology, 2015Co-Authors: Tatjana Djukic, Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Marija Matic, Tatjana Simic, Sonja Suvakov, Tatjana Pekmezovic, Ivana Novakovic, Dejan DragicevicAbstract:Purpose To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer. Methods Case–control study consisting of 187 patients with histologically confirmed transitional cell carcinoma (TCC) of urinary bladder and 140 age- and gender-matched cancer-free controls was carried out. Genotyping of GSTO1 and GSTO2 was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Results We found that carriers of mutant GSTO2 *G/G genotype were at increased risk of the development of TCC (OR 2.6, 95 % CI 1.2–5.8, p = 0.041), while GSTO1 rs4925 polymorphism was not significantly associated with TCC risk ( p = 0.450). According to smoking status, smokers with GSTO2 *G/G genotype had significantly higher risk of TCC of urinary bladder (OR 4.3, 95 % CI 1.6–11.2, p = 0.003) compared to wild-type carriers with no smoking history. We further analyzed the effects of GSTO1 / GSTO2 haplotypes on TCC risk, based on the linkage disequilibrium found for GSTO1 (rs4925) and GSTO2 (rs156697) ( D ′ = 0.309, p = 0.001). The study subjects with GSTO1 *C/ GSTO2 *G ( GSTO1 wild-type/ GSTO2 mutant) haplotype were at the highest risk of the development of transitional cell carcinoma of urinary bladder (OR 2.8, 95 % CI 1.5–5.2, p = 0.002). Conclusions Our results indicate that GSTO1 *C/ GSTO2 *G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2 *G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking.
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GSTO1*C/GSTO2*G haplotype is associated with risk of transitional cell carcinoma of urinary bladder
International urology and nephrology, 2015Co-Authors: Tatjana Djukic, Tanja Radic, Vesna Coric, Marija Pljesa-ercegovac, Marija Matic, Tatjana Simic, Sonja Suvakov, Tatjana Pekmezovic, Ivana Novakovic, Dejan DragicevicAbstract:Purpose To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer.
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gsto1 c GSTO2 g haplotype is associated with risk of transitional cell carcinoma of urinary bladder
International Urology and Nephrology, 2015Co-Authors: Tatjana Djukic, Tanja Radic, Vesna Coric, Marija Matic, Tatjana Simic, Sonja Suvakov, Tatjana Pekmezovic, Ivana Novakovic, Marija Pljesaercegovac, Dejan DragicevicAbstract:Purpose To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer.
