Enhanced Sensitivity to Oxidant-Induced Micronucleus Frequency in Elderly Individuals Is Not Associated with Glutathione S- Transferase M1 (GSTM1) Null Genotype in Lymphocytes

Gerontology ◽  
2004 ◽  
Vol 51 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Gulgun S. Guven ◽  
Mehmet Guven ◽  
Ilhan Onaran ◽  
Aydın Tunckale ◽  
Seniha Hacihanefioglu ◽  
...  
Keyword(s):  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
Elderly Individuals ◽  
Micronucleus Frequency ◽  
Enhanced Sensitivity

scholarly journals Polymorphisms and endometriosis: a systematic review and meta-analyses

2019 ◽  
Vol 26 (1) ◽  
pp. 73-103 ◽  
Author(s):  
Loren Méar ◽  
Marie Herr ◽  
Arnaud Fauconnier ◽  
Charles Pineau ◽  
François Vialard
Keyword(s):  
Systematic Review ◽  
Growth Factor ◽  
Meta Analysis ◽  
Significant Trend ◽  
Reproductive Age ◽  
Screening Tests ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
Women Of Reproductive Age ◽  
Ca Repeat

Abstract BACKGROUND Endometriosis is an estrogen-dependent gynecological disorder that affects at least 10% of women of reproductive age. It may lead to infertility and non-specific symptoms such as chronic pelvic pain. Endometriosis screening and diagnosis are difficult and time-consuming. Late diagnosis (with a delay ranging from 3.3 to 10.7 years) is a major problem and may contribute to disease progression and a worse response to treatment once initiated. Efficient screening tests might reduce this diagnostic delay. As endometriosis is presumed to be a complex disease with several genetic and non-genetic pathogenic factors, many researchers have sought to identify polymorphisms that predispose to this condition. OBJECTIVE AND RATIONALE We performed a systematic review and meta-analysis of the most regularly reported polymorphisms in order to identify those that might predispose to endometriosis and might thus be of value in screening. SEARCH METHODS The MEDLINE database was searched for English-language publications on DNA polymorphisms in endometriosis, with no date restriction. The PubTator text mining tool was used to extract gene names from the selected publications’ abstracts. We only selected polymorphisms reported by at least three studies, having applied strict inclusion and exclusion criteria to their control populations. No stratification based on ethnicity was performed. All steps were carried out according to PRISMA guidelines. OUTCOMES The initial selection of 395 publications cited 242 different genes. Sixty-two genes (corresponding to 265 different polymorphisms) were cited at least in three publications. After the application of our other selection criteria (an original case-control study of endometriosis, a reported association between endometriosis and at least one polymorphism, data on women of reproductive age and a diagnosis of endometriosis in the cases established by surgery and/or MRI and confirmed by histology), 28 polymorphisms were eligible for meta-analysis. Only five of the 28 polymorphisms were found to be significantly associated with endometriosis: interferon gamma (IFNG) (CA) repeat, glutathione S-transferase mu 1 (GSTM1) null genotype, glutathione S-transferase pi 1 (GSTP1) rs1695 and wingless-type MMTV integration site family member 4 (WNT4) rs16826658 and rs2235529. Six others showed a significant trend towards an association: progesterone receptor (PGR) PROGINS, interCellular adhesion molecule 1 (ICAM1) rs1799969, aryl-hydrocarbon receptor repressor (AHRR) rs2292596, cytochrome family 17 subfamily A polypeptide 1 (CYP17A1) rs743572, CYP2C19 rs4244285 and peroxisome proliferator-activated receptor gamma (PPARG) rs1801282), and 12 showed a significant trend towards the lack of an association: tumor necrosis factor (TNF) rs1799964, interleukin 6 (IL6) rs1800796, transforming growth factor beta 1 (TGFB1) rs1800469, estrogen receptor 1 (ESR1) rs2234693, PGR rs10895068, FSH receptor (FSHR) rs6166, ICAM1 rs5498, CYP1A1 rs4646903, CYP19A1 rs10046, tumor protein 53 (TP53) rs1042522, X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) rs25487 and serpin peptidase inhibitor clade E member 1 (SERPINE1) rs1799889; however, for the 18 polymorphisms identified in the latter two groups, further studies of the potential association with the endometriosis risk are needed. The remaining five of the 28 polymorphisms were not associated with endometriosis: glutathione S-transferase theta 1 (GSTT1) null genotype, vascular endothelial growth factor alpha (VEGFA) rs699947, rs833061, rs2010963 and rs3025039. WIDER IMPLICATIONS By carefully taking account of how the control populations were defined, we identified polymorphisms that might be candidates for use in endometriosis screening and polymorphisms not associated with endometriosis. This might constitute the first step towards identifying polymorphism combinations that predispose to endometriosis (IFNG (CA) repeat, GSTM1 null genotype, GSTP1 rs1695, WNT4 rs16826658 and WNT4 rs2235529) in a large cohort of patients with well-defined inclusion criteria. In turn, these results might improve the diagnosis of endometriosis in primary care. Lastly, our present findings may enable a better understanding of endometriosis and improve the management of patients with this disease.

Glutathione S-Transferase Gene Polymorphism and Heart Iron Overload in Thalassemia Major.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2767-2767
Author(s):  
Raffaella Origa ◽  
Stefania Satta ◽  
M. Dolores Cipollina ◽  
Lucia Perseu ◽  
Annalisa Agus ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Thalassemia Major ◽  
Myocardial Iron ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
Body Iron ◽  
Cardiac Iron ◽  
Iron Load ◽  
Allelic Distribution

Abstract Heart is the target lethal organ for iron accumulation in thalassemia major. Currently, magnetic resonance imaging (MRI) is the only non-invasive method with the potential to assess myocardial iron. MRI T2* has proven to be a fast, simple, robust and clinically useful tool for the assessment of cardiac iron load. In chelated patients, myocardial iron is usually inversely related to compliance with chelation while there is no meaningful correlation with liver iron and serum ferritin concentration measured at the time of T2* assessment. However, in a subset of patients, myocardial iron overload occurs despite an history of good compliance with chelation therapy, suggesting the possible role of genetic factors. Several gene polymorhisms including apolipoprotein epsylon and HLA haplotypes have been described as protective or predisposing factors for cardiac iron dysfunction. Wu et al. (2006) analyzed polymorphisms of two endogenous antioxidant enzymes, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1). They found that the GSTM1 null (deleted) genotype was associated with a decreased signal intensity ratio on MRI, suggesting that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition. The aim of the current study was to evaluate if the GSTM1 null genotype is a predisposing factor for myocardial iron overload in thalassemia major patients on chelation treatment with desferrioxamine with low body iron load as assessed by serum ferritin levels. Allelic distribution of wild and null GSTM1 genotype was assessed in 24 patients with thalassemia major in whom the severe myocardial iron overload (T2* <10 msec) was unexpected based on low body iron load (mean of lifelong serum ferritin determinations 1360 ± 268 ng/ml), and in 26 thalassemia patients in whom the myocardial iron overload was expected based on high body iron load (mean of lifelong serum ferritin determinations 4724 ± 1530 ng/ml). Twenty-six healthy subjects were analyzed as controls. We found that the GSTM1 null genotype was more frequent in thalassemia patients with unexpected myocardial iron load (p=0.02) than in patients with expected myocardial iron load (Table 1). The presence of the GSTM1 null genotype can therefore explain in part the development of severe myocardial iron overload in thalassemia major patients who have been adequately chelated since their first years of life. Based on the inhibition of the cardiac ryanodine receptor calcium channels by members of the glutathione transferase structural family, and given the little difference in permeability among divalent cations in those channels, we hypothesized that the deletion of GSTM1 is associated with increased entry of iron into the myocites, in patients with thalassemia major. Further studies are needed to understand the mechanisms that underlie the association between GSTM1 gene polymorphisms and predisposition to myocardial iron overload. Table 1. Allelic distribution of wild and null GSTM1 genotype in beta thalassemia patients with expected and unexpected heart iron overload, and in 26 healthy controls GSTM1 wild GSTM1 wild GSTM1 null GSTM1 null n % n % χ2 test : A vs C p>0.05; A vs B p=0.02; B vs C p=0.04 A. Thalassemic patients with expected heart iron overload 17 65.4 9 34.6 B. Thalassemic patients with unexpected heart iron overload 8 33.3 16 61.5 C. Healthy controls 16 61.5 10 38.4

Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation

Blood ◽  
2004 ◽  
Vol 104 (5) ◽  
pp. 1574-1577 ◽  
Author(s):  
Alok Srivastava ◽  
Balasubramanian Poonkuzhali ◽  
Ramachandran V. Shaji ◽  
Biju George ◽  
Vikram Mathews ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Thalassemia Major ◽  
T Test ◽  
Pharmacokinetic Analysis ◽  
P Value ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
The Impact

Abstract Hepatic venoocclusive disease (HVOD) in bone marrow transplantation (BMT) is attributed to toxicity of cytoreductive agents, especially busulfan and cyclophosphamide, in the conditioning therapy. Busulfan, as well as the metabolites of cyclophosphamide, are conjugated with glutathione (GSH), catalyzed by enzymes of the glutathione S-transferase (GST) family. To assess the impact of polymorphisms of the GST genes, GSTM1 and GSTT1, on the risk of HVOD, we evaluated 114 consecutive patients with β-thalassemia major undergoing BMT. There was a significantly increased incidence of HVOD in patients with the GSTM1-null genotype compared with those with the GSTM1-positive genotype (46.5% vs 18.3%; P = .001). Pharmacokinetic analysis in these patients showed that the clearance of busulfan was higher and first-dose steady-state concentration was lower among those with HVOD (0.403 ± 0.06 vs 0.33 ± 0.071 L/h/kg, Student t test P value = .000 01; and 508 ± 125 vs 656 ± 255 ng/mL, t test P value = .001, respectively). We conclude that the GSTM1-null genotype predisposes to HVOD, and the sinusoidal endothelial cells and hepatocyte damage may be mediated by metabolites of busulfan through depletion of the cellular GSH pool.

Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy

2002 ◽  
Vol 18 (6) ◽  
pp. 289-296 ◽  
Author(s):  
Ahmad Ahmadi ◽  
Pia Jönsson ◽  
Ulf Flodin ◽  
Peter Söderkvist
Keyword(s):  
Risk Ratio ◽  
Disease Status ◽  
Toxic Encephalopathy ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
Gstt1 Null Genotype ◽  
Increased Risk ◽  
Binomial Regression ◽  
Glutathione S Transferases ◽  
Chronic Toxic Encephalopathy

Exposure to organic solvents is still common in industrial and other work environments, and increases the risk of chronic toxic encephalopathy (CTE). Genetic variation in metabolic enzymes for solvents and other xenobiotics may modify the risk of developing toxic effects. Therefore, we investigated the presence of null genotypes for glutathione S-transferases M1 and T1 (GSTM1, GSTT1) and two genetic polymorphisms of microsomal epoxide hydrolase (mEPHX) in relation to the risk for chronic toxic encephalopathy (CTE) when exposed to solvents and smoking. We genotyped 115 patients who were classified into three categories: CTE (n3/4-56), incipient CTE (n3/4-27) and non-CTE (n3/4-32) patients. DNA was isolated from leucocytes and the GSTM1 and GSTT1 null genotypes were determined by multiplex-polymerase chain reaction. The two polymorphisms of mEPHX were analysed by PCR-RFLP (restriction fragment length polymorphism) based assays. All analyses were performed blindly with regard to both exposure and disease status. An increased binomial regression risk ratio3/4-2.5, 95% confidence interval (CI) 1.5-4.2, of the GSTM1 null genotype for CTE was found in smokers and for the GSTT1 null genotype (binomial regression risk ratio 1.5, 95% CI 1.0-2.0). In nonsmokers, the GSTM1 null genotype did not confer any risk for CTE. None of the studied mEPHX polymorphisms were associated with an increased risk for CTE. We suggest that the GSTM1 null genotype in smokers is a possible risk for solvent-induced CTE.

scholarly journals Glutathione S-Transferase Genotype polymorphism and Primary Open-Angle Glaucoma in an Italian population

2018 ◽  
Author(s):  
Sergio C Saccà ◽  
Carlo A Cutolo ◽  
Stefano Gandolfi ◽  
Giorgio Marchini ◽  
Luciano Quaranta ◽  
...  
Keyword(s):  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Italian Population ◽  
Open Angle ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
And Gender ◽  
Control Study ◽  
Gstm1 Genotype

AbstractPurposeOxidative damage to the trabecular meshwork (TM) represents one of the pathogenic mechanisms leading to primary open angle glaucoma (POAG). Glutathione S-transferase mu 1 (GSTM1) may neutralizes reactive oxygen species protecting the TM. The present paper investigates the prevalence of GSTM1 null genotype in an Italian population, and its association with POAG treated either medically or surgically.MethodsIn a case-control study, the GSTM1 genotype was identified in POAGs and controls. The POAGs patients were divided in two groups: medical POAGs and surgical POAGS. Medical POAGs consisted of patients with a well-controlled intraocular pressure (IOP) by IOP-lowering medications and a stable visual field (VF). Patients with an uncontrolled IOP and a progressing VF that were submitted to incisional surgery formed the surgical POAGs’ group.ResultsWe enrolled 104 medical POAGs, 158 surgical POAGs and 263 Controls. No significative differences between the groups existed regarding age and gender (p=0.275 and p=0.950, respectively). All the enrolled subjects were Caucasian of Italian descents. The GSTM1 null genotype was identified in 57 (45.2%) medical POAGs, 91 (57.6%) surgical POAGs and, 119 (45.3%) controls (p=0.033). The association between medical POAG and GSTM1 null status was non-significant (OR= 1.44, 95% IC = 0.86 to 2.39) whereas the association was significant for surgical POAGs (OR= 2.01, 95% IC= 1.26 to 3.21)ConclusionsOur results showed an association between the GSTM1 null genotype and glaucoma that require surgery in an Italian population. GSTM1 null genotype detection may help to identify high-risk glaucoma patients that require a closer follow-up and a more aggressive treatments.

Glutathione S-transferase (GSTM1) null genotype and sulphonamide intolerance in acquired immunodeficiency syndrome

1997 ◽  
Vol 7 (6) ◽  
pp. 519-520 ◽  
Author(s):  
Claudine Delomenie ◽  
Pascale Mathelier-Fusade ◽  
Sandrine Longuemaux ◽  
Willy Rozenbaum ◽  
Francisque Leynadier ◽  
...  
Keyword(s):  
Acquired Immunodeficiency Syndrome ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

scholarly journals Prenatal Exposure to Parabens Affects Birth Outcomes through Maternal Glutathione S-Transferase (GST) Polymorphisms: From the Mothers and Kids Environmental Health (MAKE) Study

2021 ◽  
Vol 18 (6) ◽  
pp. 3012
Author(s):  
Bohye Shin ◽  
Jeoung A. Kwon ◽  
Eun Kyo Park ◽  
Sora Kang ◽  
Seyoung Kim ◽  
...  
Keyword(s):  
Birth Weight ◽  
Birth Outcomes ◽  
Prenatal Exposure ◽  
Generalized Linear Model ◽  
Interactive Effect ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
Propyl Paraben ◽  
Gst Polymorphisms ◽  
Gstt1 Genotype

Introduction: Human exposure to parabens is very common in daily life, and prenatal exposure to these chemicals is associated with poor birth outcomes. Therefore, the aim of this study was to investigate the effect of glutathione S-transferase (GST) polymorphisms on the association between prenatal exposure to parabens and birth outcomes. Methods: We conducted a multivariate analysis involving 177 subjects to determine the association between paraben concentrations and birth outcomes in mothers with GST mu 1 (GSTM1) and GST theta 1 (GSTT1) polymorphisms from 2017 to 2019. Furthermore, we determined the interactive effect between paraben levels and GSTM1/GSTT1 polymorphisms using regression analysis, in addition to a generalized linear model after stratifying GSTM1/GSTT1 genotype into three categories. Results: Methyl and propyl paraben concentrations were significantly and positively associated with birth weight (methyl, β = 116.525, 95% confidence interval (CI) = 22.460–210.590; propyl, β = 82.352, 95% CI = 9.147–155.557) in individuals with the GSTM1-null genotype. Moreover, the propyl paraben concentration was significantly associated with an increase in gestational age (β = 0.312, 95% CI = 0.085–0.539) in individuals with the GSTM1-null genotype. Conclusions: This study reported the association between prenatal paraben exposure and birth outcomes in individuals with GST polymorphisms. We found positive relationships of maternal exposure to methyl parabens with birth weight in both mothers with GSTM1 and GSTT1-null genotypes.

scholarly journals An Updated Meta-Analysis: Risk Conferred by Glutathione S-Transferases (GSTM1andGSTT1) Polymorphisms to Age-Related Cataract

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Rong-feng Liao ◽  
Min-jie Ye ◽  
Cai-yuan Liu ◽  
Dong-qing Ye
Keyword(s):  
Meta Analysis ◽  
Pooled Analysis ◽  
Protective Role ◽  
Gstm1 Null Genotype ◽  
Ethnic Variation ◽  
Glutathione S Transferase ◽  
Gstt1 Null Genotype ◽  
Age Related ◽  
Increased Risk ◽  
Glutathione S Transferases

Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC).Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included.Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057–1.429, andP=0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598–0.850, andP<0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137–1.830, andP=0.003) but not in Caucasians.Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians.

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