Glutathione S-transferase Theta-1 Gene Research Articles

Glutathione S-transferase M1 and T1 gene polymorphisms in psoriasis patients: a pilot case-control study

Background The exact etiology of psoriasis remains unknown; nevertheless, it has been found that oxidative stress plays a vital role. Among the multiple antioxidant enzymes, genetic polymorphisms in the Glutathione S-Transferases (GSTs) led to an imbalance in the antioxidant system, resulting in increased levels of reactive oxygen species. Accordingly, the polymorphism in these genes could increase the susceptibility to psoriasis. Objectives To assess the association between Glutathione S-Transferase M1 (GSTM1) and Glutathione S Transferase Theta-1 (GSTT1) gene polymorphisms in psoriasis patients compared to healthy controls. Methods A total of 200 participants, 100 psoriasis cases who were assessed by the Psoriasis Area and Severity Index (PASI), and 100 healthy controls were included. DNA extraction was done followed by multiplex PCR to detect genetic polymorphism in the GSTM1 and GSTT1 genes, Finally, the relation between the presence of polymorphism and the severity of psoriasis was estimated. Results The null genotype frequency of GSTM1 and GSTT1 was 76.0% and 58.0%, respectively among psoriasis patients, while it was 58.0% and 55.0%, respectively among healthy controls. There was a significantly higher risk for psoriasis in patients with the null genotype GSTM1 (OR=2.293) as compared to controls. On the other hand, there was no statistically significant relation between their polymorphisms and family history, psoriasis severity, and PASI score. Conclusion The null genotype GSTM1 could increase the risk of psoriasis susceptibility especially among males.

GSTT1 PROMOTES OSTEOGENIC DIFFERENTIATION OF ADIPOSE STEM CELLS

We found that adipose stem cells are poorly differentiated into bone and that their ability to differentiate into bone varies from cell line to cell line. The osteogenic differentiation ability of the adipose stem cell lines was distinguished through Alzarin Red Staining, and the cell lines that performed well and those that did not were subjected to RNA-seq analysis. The selected gene GSTT1 (glutathione S-transferase theta-1) gene is a member of a protein superfamily that catalyzes the conjugation of reduced glutathione to a variety of hydrophilic and hydrophobic compounds. The purpose of this study is to treat avascular necrosis and bone defect by improving bone regeneration with adipose stem cells introduced with a new GSTT1 gene related to osteogenic differentiation of adipose stem cells. In addition, the GSTT1 gene has the potential as a genetic marker that can select a specific cell line in the development of an adipose stem cell bone regeneration drug.Total RNA was extracted from each sample using the TRIzol reagent. Its concentration and purity were determined based on A260 and A260/A280, respectively, using a spectrophotometer. RNA sequencing library of each sample was prepared using a TruSeq RNA Library Prep Kit. RNA-seq experiments were performed for hADSCs. Cells were transfected with either GSTT1 at 100 nM or siControl (scramble control) by electroporation using a 1050 pulse voltage for 30 ms with 2 pulses using a 10 μl pipette tip.The purpose of this study is to discover genetic markers that can promote osteogenic differentiation of adipose stem cells (hADSCs) through mRNA-seq gene analysis. The selected GSTT1 gene was found to be associated with the enhancement of osteogenic differentiation of adipose stem cells. siRNA against GSTT1 reduced osteogenic differentiation of hADSCs, whereas GSTT1 overexpression enhanced osteogenic differentiation of hADSCs under osteogenic conditions.In this study, GSTT1 transgenic adipose stem cells could be used in regenerative medicine to improve bone differentiation. In addition, the GSTT1 gene has important significance as a marker for selecting adipose stem cells with potential for bone differentiation in the development of a therapeutic agent for bone regeneration cells.

Air pollution associated acute respiratory inflammation and modification by GSTM1 and GSTT1 gene polymorphisms: a panel study of healthy undergraduates

Epidemiological evidence has linked air pollution with adverse respiratory outcomes, but the mechanisms underlying susceptibility to air pollution remain unclear. This study aimed to investigate the role of glutathione S-transferase (GST) polymorphism in the association between air pollution and lung function levels. A total of 75 healthy young volunteers aged 18–20 years old were recruited for six follow-up visits and examinations. Spirometry was conducted to obtain lung function parameters such as forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1). Nasal fluid concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and 8-epi-prostaglandin F2α (8-epi-PGF2a) were measured using ELISA kits. Linear mixed-effect models were used to evaluate the association of air pollutants with respiratory outcomes. Additionally, polymorphisms of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) were estimated to explore its role in the association between air pollutants and lung function. We found that short-term exposure to atmospheric particulates such as PM2.5 and PM10 can cause an increase in nasal biomarkers of inflammation, oxidative stress, and lung function, while air gaseous pollutant exposure is linked with decreased lung function, except for CO. Stratification analyses showed that an increase in nasal inflammatory cytokines caused by exposure to atmospheric particulates is more obvious in subjects with GSTM1-sufficient (GSTM1+) than GSTM1-null (GSTM1−), while elevated lung function levels due to air particles are more significant in subjects with the genotype of GSTM1− when compared to GSTM1+. As for air gaseous pollutants, decreased lung function levels caused by O3, SO2, and NO2 exposure is more manifest in subjects with the genotype of GSTM1− compared to GSTM1+. Taken together, short-term exposure to air pollutants is associated with alterations in nasal biomarkers and lung function levels in young healthy adults, and susceptible genotypes play an important mediation role in the association between exposure to air pollutants and inflammation, oxidative stress, and lung function levels.

Worldwide Systematic Review of GSTM1 and GSTT1 Null Genotypes by Continent, Ethnicity, and Therapeutic Area.

Glutathione S-transferase Mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) enzymes are glutathione-S-transferases with broad significance for susceptibility or resistance to multifactorial human diseases, as well as detoxification of environmental chemicals and drugs. Moreover, some individuals may have a complete deletion of GSTM1 and GSTT1 genes, which can contribute to patient-to-patient variability in drug safety and efficacy. GSTM1 and GSTT1 gene deletion frequencies can vary according to ethnicity and continental origin of the studied population with implications for achieving the goal of precision/personalized medicine in clinical practice. We report here a worldwide systematic review of the null genotypes in these two clinically important genes by continents, ethnicities, and therapeutic areas (TAs). Searches were performed in the PubMed database covering the period from 1992 to 2020. Out of the 1925 articles included, most studies analyzed European individuals, corroborating the literature failure for not adequately considering the non-European ethnicities. The frequency of GSTM1 and GSTT1 null genotypes was higher in patients than in healthy volunteers. Conversely, in East Asians, higher frequencies of the null genotypes were observed in healthy volunteers than patients. Oncology was the most intensively studied TA (57% of the articles) in relation to GSTM1 and GSTT1. In all, these results demonstrate that there is an important gap in the literature in terms of failure to consider a broader range of populations, as well as diseases wherein GSTM1 and GSTT1 variations have clinical and biological implications. To achieve precision/personalized medicine on a global/worldwide scale, with equity and inclusiveness, this knowledge/research gap ought to be remedied in studies of GSTM1 and GSTT1 null genotypes. To the best of our knowledge, this is the largest systematic review conducted to date addressing the GSTM1 and GSTT1 null genotypes worldwide. The analyses from the 1925 articles highlighted the current knowledge gaps in different TAs, ethnicities, and populations. Filling these gaps is of importance, given the role these genes play in relation to the metabolism of substances to which we have frequent contact with, the associations observed between their deletion and diseases such as cancer, in addition to the interethnic differences observed for the deletion frequencies of these genes.

Investigation of the Relationship between Genetic Polymorphisms in GSTM1 and GSTT1 Genes and Susceptibility to Lung Functional Abnormalities in Workers Exposed to Air Pollutants at Isfahan Steel Plant

Introduction: Gaseous air pollutants can cause oxidative stress, which can lead to lung damage by inducing inflammation. Polymorphisms in the glutathione S-transferase (GST) gene are involved in the pathogenesis of many diseases, including lung disease. Two glutathione S-transferase Mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) genes belong to this family, in which deletions occur and the resulting alleles are unable to produce active enzymes.
 Materials and Methods: In this study, 41 steel plant workers with impaired lung function were selected. Multiplex PCR technique was used to identify the genotyping of GST M1 and T1.
 Results: The results of the frequency of gene deletion among 41 patients showed that there were 10 individuals (17.2%) with deletion of GSTM1 gene, 4 individuals (11.8%) with deletion of GSTT1 gene. The results of the frequency of gene deletion among 50 healthy individuals (control group) also showed that there were 8 individuals (8.5%) with deletion of GSTM1 gene, and 12 individuals (8.3%) with deletion of GSTT1 gene. There were 7 individuals (14%) without deletion of GSTM1 and GSTT1 removal. The results of Chi-square test between healthy and sick groups showed no significance at the level of p < 0.05.
 Conclusion: According to the results, it can be concluded that the sensitivity to lung function abnormalities in steel workers is directly related to the duration of employment.

Role of Glutathione S-Transferase M1 and Glutathione S Transferase Theta 1 Gene Polymorphism, Histopathological, and Immunohistochemistry in Carcinoma Breast

Background:Breast cancer is the most common invasive cancer in females in developing countries such as India. It is the most common malignancy in females in the Punjab state.Objectives:(1) The purpose of this study was to calculate the prevalence of the four subtypes of breast cancer based on molecular classification and (2) to determine the association of polymorphisms in Glutathione S-Transferase M1 (GSTM1) and Glutathione S transferase theta 1 (GSTT1) gene in carcinoma of the breast with histopathological grading.Materials and Methods:This study analyzed histologically confirmed 100 cases of carcinoma breast; immunohistochemistry and reverse transcription polymerase chain reaction molecular tests were performed for further grading, molecular typing, and gene polymorphism.Results:Out of 24 Grade I tumors, 18 (75.00%) expressed the GSTM1 gene and 6 (25.00%) were negative. Out of 48 Grade II tumors, 30 (62.50%) expressed the GSTM1 gene and 18 (37.50%) were negative. Out of 28 Grade III tumors, 8 (28.57%) expressed the GSTM1 gene and 20 (71.43%) were negative. Out of 24 Grade I tumors, 17 (70.83%) expressed the GSTT1 gene and 7 (29.17%) were negative. Out of 48 Grade 2 tumors, 28 (58.33%) expressed the GSTT1 gene and 20 (41.67%) were negative. Out of 28 Grade III tumors, 8 (28.57%) expressed the GSTT1 gene and 20 (71.43%) were negative.Conclusion:Our study shows that polymorphism of both GSTM1 and GSTT1, either individually or in combination, influences the risk of developing carcinoma due to DNA damage caused by many factors including environmental and genetic.

Association of Polymorphisms in the Glutathione S-Transferase Theta-1 Gene with Cirrhosis and Hepatocellular Carcinoma in Brazilian Patients with Chronic Hepatitis C.

Oxidative stress contributes to hepatitis C virus (HCV)–induced liver damage. Host genetic factors may be involved in progression of HCV infection. The present study was conducted to determine the influence of glutathione S-transferase (GST)-M1 and T1 gene polymorphisms during different stages of HCV infection, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The study population comprised 190 patients (47 with chronic hepatitis, 83 with cirrhosis (without HCC), and 60 with HCC). GSTM1 and GSTT1 gene polymorphisms were analyzed via multiplex polymerase chain reaction. The GSTT1-null genotype was more commonly detected in patients with cirrhosis (n = 17; 20.5%) and HCC (n = 13; 21.7%) than those with chronic hepatitis (n = 3; 6.4%). The differences in GSTT1-null genotype frequencies were significant for cirrhosis vs. chronic hepatitis (odds ratio, OR, 3.778 (95% confidence interval, CI, 1.045–13.659); p = 0.043) and HCC vs. chronic hepatitis (OR, 4.057 (95% CI, 1.083–15.201); p = 0.038) groups. However, the incidence of individual GSTM1-null or combined GSTM1/GSTT1 double-null genotypes did not vary significantly between the groups. Our collective findings support the utility of the GSTT1-null genotype as a useful biomarker for liver disease progression in Brazilian patients with chronic hepatitis C.

Interindividual Differences in DNA Adduct Formation and Detoxification of 1,3-Butadiene-Derived Epoxide in Human HapMap Cell Lines.

Smoking-induced lung cancer is a major cause of cancer mortality in the US and worldwide. While 11-24% of smokers will develop lung cancer, risk varies among individuals and ethnic/racial groups. Specifically, African American and Native Hawaiian cigarette smokers are more likely to get lung cancer as compared to Caucasians, Japanese Americans, and Latinos. It is important to identify smokers who are at the greatest risk of developing lung cancer as they should be candidates for smoking cessation and chemopreventive intervention programs. Among 60+ tobacco smoke carcinogens, 1,3-butadiene (BD) is one of the most potent and abundant (20-75 μg per cigarette in mainstream smoke and 205-361 μg per cigarette in side stream smoke). BD is metabolically activated to 3,4-epoxy-1-butene (EB), which can be detoxified by glutathione S-transferase theta 1 (GSTT1)-mediated conjugation with glutathione, or can react with DNA to form 7-(1-hydroxy-3-buten-2-yl)guanine (EB-GII) adducts. In the present study, we employed EBV-transformed human lymphoblastoid cell lines (HapMap cells) with known GSTT1 genotypes to examine the influence of the GSTT1 gene on interindividual variability in butadiene metabolism, DNA adduct formation/repair, and biological outcomes (apoptosis). We found that GSTT1- HapMap cells treated with EB in culture produced lower levels of glutathione conjugates and were more susceptible to apoptosis but had similar numbers of EB-GII adducts as GSTT1+ cells. Our results suggest that GSTT1 can influence an individual's susceptibility to butadiene-derived epoxides.

P105 Glutathione S-transferase theta 1 protects against colitis through goblet cell differentiation via interleukin-22

Abstract Background The enzyme glutathione S-transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Oxidative stress plays a key role in the pathogenesis of inflammatory bowel disease (IBD). Although mutation of the GSTT1 gene increases IBD susceptibility, the underlying mechanisms remain unexplained. Methods The Gstt1 gene was intrarectally or intraperitoneally delivered to mice with dextran sodium sulphate (DSS)-induced colitis. The GSTT1 gene was knocked down or knocked out using short interfering RNA or genome editing, respectively. Protein and mRNA expression and differentiation of goblet cells were evaluated. Results We identified decreased expression of GSTT1 in inflamed tissues from IBD patients and mice compared with their control counterparts, respectively. We also noted attenuation of colitis through gene transfer of Gstt1 to DSS-treated mice via the interleukin-22 (IL-22) pathway. GSTT1 was differently regulated by pathogens and host immune responses. Down-regulation of GSTT1 reduced innate defence responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells as well as IBD patients diminished its dimerisation, which was connected to insufficient phosphorylation of signal transducer and activator of transcription 3 and p38/mitogen-activated protein kinase by their common activator, IL-22. Conclusion GSTT1 ameliorated IL-22 in colitis in a dependent manner and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerisation. Our results provide new insights into GSTT1 mutations and their functional consequences in IBDs.

Association of glutathione S‐transferase theta 1 and glutathione S‐transferase mu 1 gene polymorphism with the risk of pre‐eclampsia during pregnancy in Bangladesh

In this study, we analyzed the risk of developing pre-eclampsia with respect to glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1 (GSTM1) genotypes. We also tried to find relationship between genotypes and biochemical parameter change in pre-eclampsia patients. In total, 104 pre-eclampsia patients and 200 healthy controls were recruited for the study. Peripheral venous blood was drawn from study subjects and DNA was extracted from whole blood and multiplex polymerase chain reaction method was used to identify genotypes of GSTT1 and GSTM1 gene. All biochemical parameters were measured using colorimetric method. Serum glutamic pyruvic transaminase level was significantly higher (P < 0.01) and hemoglobin level was significantly lower (P < 0.001) in pre-eclampsia patients compared to control subjects. Significant association was found in GSTM1 null genotype with pre-eclampsia (P < 0.001) with an odds ratio (OR) analysis showing more than four-fold increased risk (OR = 4.75; 95% CI = 2.17-10.39; P <0.001). But for GSTT1 gene, null genotype was not associated with increased risk of developing pre-eclampsia (P > 0.05). In case of GSTT1 and GSTM1, the patients having both null genotypes for GSTT1 and GSTM1 showed significant (P < 0.001) higher risk of developing pre-eclampsia (OR = 7.64; 95% CI = 2.38-24.60; P < 0.001). GSTM1 null genotype increases the risk of pre-eclampsia. Combined GSTT1 and GSTM1 null genotype, the risk was even higher.

Arginine intake is associated with oxidative stress in a general population

ObjectiveThe aim of this study was to assess the association between protein and arginine from meat intake and oxidative stress in a general population. MethodsData came from the Health Survey for Sao Paulo (ISA-Capital), a cross-sectional population-based study in Brazil (N = 549 adults). Food intake was estimated by a 24-h dietary recall. Oxidative stress was estimated by malondialdehyde (MDA) concentration in plasma. Analyses were performed using general linear regression models adjusted for some genetic, lifestyle, and biochemical confounders. ResultsMDA levels were associated with meat intake (P for linear trend = 0.031), protein from meat (P for linear trend = 0.006), and arginine from meat (P for linear trend = 0.044) after adjustments for confounders: age, sex, body mass index, smoking, physical activity, intake of fruit and vegetables, energy and heterocyclic amines, C-reactive protein levels, and polymorphisms in GSTM1 (glutathione S-transferase Mu 1) and GSTT1 (glutathione S-transferase theta 1) genes. Results were not significant for total protein and protein from vegetable intake (P > 0.05). ConclusionsHigh protein and arginine from meat intake were associated with oxidative stress independently of genetic, lifestyle, and biochemical confounders in a population-based study. Our results suggested a novel link between high protein/arginine intake and oxidative stress, which is a major cause of age-related diseases.

Genotypes of GSTM1 and GSTT1: Useful determinants for clinical outcome of bladder cancer in Pakistani population

BackgroundIncidence of bladder cancer has increased rapidly worldwide in the past few years. Environmental as well as genetic factors are involved in the etiology of bladder cancer. Glutathione S transferase mu 1 (GSTM1) and glutathione S transferase theta 1 (GSTT1) genes are two xenobiotic metabolizing genes in phase II of detoxification process. AimThe current study was aimed to find out the association of different environmental factors and GSTM1 and GSTT1 gene polymorphisms with susceptibility to bladder cancer in Pakistani population. MethodBladder cancer cases (236) and control blood samples (270) were screened using phenol chloroform method of DNA extraction followed by multiplex PCR. ResultsWith respect to age; bladder cancer was more prevalent in age >60years and low grade tumors were more frequent than high grade tumors. Smokers had a significantly higher incidence rate of cancer; also family history of cancer was found to be strongly associated (P<0.05) with bladder cancer. Commonly reported symptoms by the patients of bladder cancer were hematuria, lower urinary tract symptoms (LUTS) and flank pain. A larger number of patients had undergone surgery, chemotherapy and radiotherapy. Similarly GSTM1 (OR 2.24; CI 1.5–3.2; P=0.0001) and GSTT1 (OR 2.9; CI 1.4–6.1; P=0.002) gene deletion showed a highly significant association with bladder cancer. Simultaneous deletions of both GSTM1 and GSTT1 genes also showed highly significant association (OR 5.3; CI 2.1–13.1; P=0.0001) with cancer risk. No association was found when both of the two genes deletion was compared with bladder cancer among smokers. ConclusionThis study suggests that GSTM1 and GSTT1 gene polymorphisms may be associated with increased susceptibility toward bladder cancer in Pakistani population.

Polymorphisms of GSTM1, GSTT1, and p53 in Goiânia, Goiás.

Genetic polymorphisms are defined as changes within the DNA sequences of genes that have frequencies in the population higher than 1%. The glutathione S-transferases play an important role in the cellular detoxification systems involved in oxidative stress that can lead to accumulation of reactive oxygen species. Epidemiological studies have suggested that individuals with homozygous deletion of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) are at higher risk of developing several types of neoplasias. The p53 protein is highly expressed in tumors and transformed cells, and the p53 is a classical tumor suppressor gene involved in regulating cell growth and development. In this study, we investigated the prevalence of polymorphisms in the p53, GSTM1, and GSTT1 genes in a population from Goiânia. We evaluated the polymorphisms of these genes in peripheral blood samples. The null or present polymorphism of GSTM1 and GSTT1 genes and Arg/Pro of the p53 gene were analyzed. Our results revealed a higher frequency of the GSTM1-null polymorphism (72.4%) than the GSTM1-present genotype (27.6%). For GSTT1, we observed higher frequency for the null genotype (65.5%) compared to the present genotype (34.5%). Analysis of p53 gene polymorphisms showed a higher frequency for the genotype Arg/Pro (66%) and a lower frequency for the Arg/Arg (23%) and Pro/Pro (11%) genotypes. It is essential to understand polymorphism frequencies in different populations and to evaluate the role of genetic polymorphisms and their effects on health.

Genetic polymorphisms of glutathione S-transferase Mu 1, glutathione S-transferase theta 1, and glutathione S-transferase P1 in oral squamous cell carcinoma: A case-control study in Iranian population

Background: Gene variability related to activation and detoxification of procarcinogens affects the susceptibility to oral squamous cell carcinoma (OSCC). The results of numerous studies investigating the interrelationship between polymorphisms of glutathione S- transferase enzymes are not conclusive and there are little data regarding this topic on Iranian population. Aims and Objectives: This study aimed to investigate the genetic polymorphisms in glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase P1 (GSTP1) and the association with the risk of OSCC in Iranian population. Materials and Methods: The genetic polymorphisms of GSTM1, GSTT1, and GSTP1 genes were investigated in 35 Iranian patients with the OSCC and 60 age-sex matched controls. GSTP1 genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism method and GSTM1 and GSTT1 genotyping was amplified with PCR using specific primers. Odds ratios (ORs) and their 95% confidence intervals (CIs) were obtained using SPSS 17 and the risk of OSCC in relation to GSTM1, GSTT1, and GSTP1 polymorphism was defined. Results: The prevalence of GSTM1 and GSTT1 null genotypes in OSCC group were significantly higher than the control group.(OR = 2.6, 95% CI = 1.04-6.5; P = 0.01 for GSTM1) (OR = 11, 95% CI = 9-31; P = 0.001 for GSTT1). The GSTP1 valine polymorphism was not significantly different between the study groups (P = 0.145). Conclusions: GSTM1 and GSTT1 null genotypes may increase the risk for OSCC development in Iranian patients.

Genetic interaction of GSH metabolic pathway genes in cystic fibrosis

BackgroundCystic fibrosis (CF) is a monogenic disease caused by CFTR gene mutations, with clinical expression similar to complex disease, influenced by genetic and environmental factors. Among the possible modifier genes, those associated to metabolic pathways of glutathione (GSH) have been considered as potential modulators of CF clinical severity. In this way it is of pivotal importance investigate gene polymorphisms at Glutamate-Cysteine Ligase, Catalytic Subunit (GCLC), Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and Glutathione S-transferase P1 (GSTP1), which have been associated to the GSH metabolic pathway and CF clinical severity.MethodA total of 180 CF’s patients were included in this study, which investigated polymorphisms in GCLC and GST genes (GCLC -129C>T and -3506A>G; GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G) by PCR and PCR-RFLP associating to clinical variables of CF severity, including variables of sex, clinical scores [Shwachman-Kulczycki, Kanga e Bhalla (BS)], body mass index, patient age, age for diagnosis, first clinical symptoms, first colonization by Pseudomonas aeruginosa, sputum’s microorganisms, hemoglobin oxygen saturation in the blood, spirometry and comorbidities. The CFTR genotype was investigated in all patients, and the genetic interaction was performed using MDR2.0 and MDRPT0.4.7 software.ResultsThe analysis of multiple genes in metabolic pathways in diseases with variable clinical expression, as CF disease, enables understanding of phenotypic diversity. Our data show evidence of interaction between the GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G polymorphism with CFTR gene mutation classes, and BS (Balance testing accuracy= 0.6824, p= 0.008), which measures the commitment of bronchopulmonary segments by tomography.ConclusionPolymorphisms in genes associated with metabolism of GSH act on the CF’s severity.

GSTM1 and GSTT1 polymorphisms in endometriosis in women from Goiás, Brazil

Endometriosis is a gynecologic pathology with a high prevalence and unknown etiology. Therefore, an increasing number of studies has been undertaken to search for associations between endometriosis and alterations or polymorphisms in candidate genes, including glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1). We analyzed the frequency of present/absent polymorphisms of GSTM1 and GSTT1 in 50 women diagnosed with endometriosis and in a control group of 46 women without complaints related to this pathology. The association of these polymorphisms with p53 gene codon 72 was also evaluated within each group, and a higher frequency of absence of GSTM1 (61%) and GSTT1 (45%) genes in the group of women studied, women with endometriosis and control group was found. The contributions of GSTM1 and GSTT1 polymorphisms to the proliferation of endometriosis were not statistically significant, but the analysis of pathology and the association of GSTM1 and GSTT1 gene polymorphisms with p53 codon 72 revealed statistical significance.

Lack of association of GSTT1 and GSTP1 genes methylation and their expression profiles with risk of NAFLD in a sample of Iranian patients

Reactive oxygen species can affect many cellular functions through protein oxidation or initiation of the lipid peroxidation cascade that can lead to non-alcoholic fatty liver disease (NAFLD), characterized by significant lipid deposition in the hepatocytes of patients with no history of excess alcohol intakes. The present study aimed to analyze the methylation status of the antioxidative stress genes GSTT1 (glutathione S-transferase theta-1) and GSTP1 (glutathione S-transferase pi-1), and their expression profiles, in a sample population of patients with NAFLD living in South-East Iran. Peripheral blood samples were obtained from 80 NAFLD patients and 80 healthy controls. Promoter methylation of the GSTT1 and GSTP1 genes were analyzed by methylation-specific polymerase chain reaction (MS-PCR). Expression profiles of these genes were also examined by quantitative real-time PCR analysis. Promoter methylation of the GSTT1 gene was detected in 86.2% of cases and in 91.2% of controls and, of the GSTP1 gene, in 88.8 and 87.5% of cases and controls, respectively. Promoter methylation of GSTT1 and GSTP1 was not statistically different in cases compared with healthy controls. Similarly, mRNA expression levels showed no statistically significant variations between healthy individuals and patients with NAFLD. Our findings indicate no association between methylation status and expression profiles of GSTT1 and GSTP1 genes and NAFLD. This is the first report to assess such associations in a sample of the Iranian population.

Estrogen receptor 1, Glutathione S-transferase P1, Glutathione S-transferase M1, and Glutathione S-transferase T1 Genes with Dysmenorrhea in Korean Female Adolescents

Dysmenorrhea is the most common gynecologic complaint among adolescent females. We investigated the association between genetic polymorphisms and dysmenorrhea. A total of 202 postmenarcheal Korean female adolescents 16-17 yr old participated in this study. Genotyping for glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), glutathione S-transferase pi 1 (GSTP1), and estrogen receptor 1 (ESR1) was performed using PCR-based methods. The PP+Pp genotype of the ESR1 gene was more frequent than pp genotypes in subjects with dysmenorrhea than in subjects without dysmenorrhea (odds ratio=2.440; 95% confidence interval, 1.036-5.753; P=0.040) using an unadjusted univariate logistic regression analysis. The relationship between dysmenorrhea and ESR1 gene polymorphisms remained significant after adjustment for premenstrual syndrome, years elapsed after menarche, and family history of dysmenorrhea. No significant difference was observed between subjects with dysmenorrhea and subjects without dysmenorrhea for polymorphisms of GSTM1, GSTT1, and GSTP1 genes. Our results suggest that ESR1 gene polymorphisms may be associated with dysmenorrhea.

Relationship between expression of mutant type glutathione S-transferase theta-1 gene and reactivity of rapamycin in myelodysplastic syndrome

We previously reported mRNA expression of glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp), in patients with myelodysplastic syndrome (MDS). The deletion of 123 bp creates a sequence that is homologous to the mammalian target of rapamycin (mTOR). To analyze the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of the wild and mutant type of the GSTT-1 gene of those stable transformants in cell lines and in bone marrow cells from MDS patients by reverse-transcription polymerase chain reaction (RT-PCR) was observed in the presence or absence of rapamycin. Significant growth inhibition by rapamycin was observed among stable transformants for the mutant GSTT-1 gene, but not wild type GSTT-1 gene, and was indicative of typical apoptosis.

Copy-Number Variation Genotyping of GSTT1 and GSTM1 Gene Deletions by Real-Time PCR

Structural variation in the human genome is increasingly recognized as being highly prevalent and having relevance to common human diseases. Array-based comparative genome-hybridization technology can be used to determine copy-number variation (CNV) across entire genomes, and quantitative PCR (qPCR) can be used to validate de novo variation or assays of common CNV in disease-association studies. Analysis of large qPCR data sets can be complicated and time-consuming, however. We describe qPCR assays for GSTM1 (glutathione S-transferase mu 1) and GSTT1 (glutathione S-transferase theta 1) gene deletions that can genotype up to 192 samples in duplicate 5-microL reaction volumes in <2 h on the ABI Prism 7900HT Sequence Detection System. To streamline data handling and analysis of these CNVs by qPCR, we developed a novel interactive, macro-driven Microsoft Excel(R) spreadsheet. As proof of principle, we used our software to analyze CNV data for 1478 DNA samples from a family-based cohort. With only 8 ng of DNA template, we assigned CNV genotypes (i.e., 2, 1, or 0 copies) to either 96% (GSTM1) or 91% (GSTT1) of all DNA samples in a single round of PCR amplification. Genotyping accuracy, as ascertained by familial inheritance, was >99.5%, and independent genotype assignments with replicate real-time PCR runs were 100% concordant. The genotyping assay for GSTM1 and GSTT1 gene deletion is suitable for large genetic epidemiologic studies and is a highly effective analysis system that is readily adaptable to analysis of other CNVs. .