Glutathione S-transferase T1 Gene Polymorphisms Research Articles

GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study.

Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S-transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross-sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(-) null genotype and COPD risk was observed (odds ratio=2.04, 95% CI=1.30-3.20, P=0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(-) null genotype and COPD risk (adjusted odds ratio=2.90, 95% CI=1.43-5.87, P=0.003). The GSTT1(-) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(-) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(-) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(-) null genotype in the North Indian population.

Glutathione S-transferase M1 and T1 polymorphisms, and their interactions with smoking on risk of low birth weight: a meta-analysis

Background: Published data regarding the association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) gene polymorphisms and risk of low birth weight (LBW) remains inconclusive, and data on the interactions between the two gene polymorphisms and smoking for LBW susceptibility is lacking. To clarify these associations, a meta-analysis was conducted.Methods: A comprehensive literature search was conducted in multiple databases until 11 January 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed or random effects model.Results: Thirty-eight studies from 17 articles concerning maternal and neonatal GSTM1 and GSTT1 gene polymorphism with LBW risk were included in this meta-analysis, and nine studies from five articles provided data of maternal tobacco exposure status during pregnancy. Maternal GSTM1 null genotype was associated with increased LBW risk (OR = 1.27, 95% CI: 1.12–1.45). There was a nonsignificant but positive association (OR = 1.19, 95% CI: 0.97–1.46) between the maternal GSTT1 null genotype and the LBW risk in the overall analysis. There was a null association between neonatal GSTM1 or GSTT1 polymorphism and LBW risk. There were significant associations between the maternal GSTM1 null and GSTT1 null genotype and LBW risk (for the former, OR = 3.85, 95% CI: 1.68–8.81; for the later, OR = 1.88, 95% CI: 1.01–3.50) in individuals with active smoking, respectively.Conclusion: Maternal GSTM1 and GSTT1 null genotypes, but not neonatal genotypes, are suggested to increase LBW susceptibility, and there are interactions between active smoking and these polymorphisms in the development of LBW.

Is There Any Association between Glutathione S-transferases M1 and Glutathione S-transferases T1 Gene Polymorphisms and Endometrial Cancer Risk? A Meta-analysis.

Epidemiological evidence on the association between genetic polymorphisms in glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes and risk of endometrial cancer (EC) has been inconsistent. In this meta-analysis, we seek to investigate the relationship between GSTM1 and GSTT1 polymorphisms and the risk of EC. We searched Medline, PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature database to identify eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) for the association were determined using a fixed- or random-effect model. Tests for heterogeneity of the results and sensitivity analyses were performed. A total of six case–control studies were included in the final meta-analysis of GSTM1 (1293 cases and 2211 controls) and GSTT1 (1286 cases and 2200 controls) genotypes. Overall, GSTM1 null genotype was not significantly associated with an increased risk of EC (OR = 1.00, 95% CI = 0.76–1.30, P = 0.982). Similarly, for GSTT1 deletion genotype, we observed no association under the investigated model in the overall analysis (OR = 0.91, 95% CI = 0.64–1.30, P = 0.619). Subgroup analysis also showed no significant association between the GSTM1 null genotype and EC risk in hospital-based design (OR = 1.26, 95% CI = 0.93–1.71, P = 0.131) and no relationship between GSTT1 null genotype with EC risk in population-based design (OR = 1.18, 95% CI = 0.79–1.76, P = 0.407). However, GSTM1 null genotype contributed to an increased EC risk in population-based design (OR = 0.76, 95% CI = 0.60–0.97, P = 0.027), while null GSTT1 in hospital-based studies (OR = 0.70, 95% CI = 0.52–0.93, P = 0.015). The present meta-analysis suggested that GSTs genetic polymorphisms may not be involved in the etiology of EC. Large epidemiological studies with the combination of GSTM1 null, GSTT1 null, and design-specific with the development of EC are needed to prove our findings.

Effects of lymphocyte DNA damage levels in Korean plant food groups and Korean diet regarding to glutathione S-transferase M1 and T1 polymorphisms

Purpose: GST (glutathione S-transferase) M1 and T1 gene polymorphisms are known to affect antioxidant levels. This study was carried out to evaluate genetic susceptibility by measuring the effect of DNA damage reduction in the Korean diet by vegetable food according to GST gene polymorphisms using the ex vivo method with human lymphocytes. Methods: Vegetable foods in the Korean diet based the results of the KNHANES V-2 (2011) were classified into 10 food groups. A total of 84 foods, which constituted more than 1% of the total intake in each food group, were finally designated as a vegetable food in the Korean diet. The Korean diet applied in this study is the standard one-week meals for Koreans (2,000 Kcal/day) suggested by the 2010 Dietary Reference Intakes for Koreans. Ex vivo DNA damage in human lymphocytes was assessed using comet assay. Results: In the Korean food group, the DNA damage protective effect of GSTM1 and GSTT1 was found to be greater in mutant type and wild-type, respectively. and the DNA damage protective effect according to the combined genotype of GSTM1 and GSTT1 was different depending on the food group. On the other hand, in Korean Diet, the DNA damage protective effect appeared to be larger in GSTM1 wild-type than in mutant type and was found to not be affected by GSTT1 genotype. Conclusion: These results can be used as basic data to demonstrate the superiority of the antioxidant function of Korean dietary patterns and food groups. Furthermore, it may be a starting point to begin research on customized antioxidant nutrition according to individual genes.

Evaluation of Genomic Damage in Peripheral Lymphocytes from Occupationally Exposed Anesthetists: Assessment of the Effects of Age, Sex, and GSTT1 Gene Polymorphism.

Occupational exposure to anaesthetic gases is one of the major hazards to healthcare personnel. We evaluated the cytogenetic effects of chronic exposure to low concentrations of anaesthetic gases in operating theatres. The study included 21 anesthetists and 21 control subjects who matched in age and gender. Chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) assays were performed. All subjects were also genotyped for glutathione S-transferase T1 (GSTT1) gene polymorphisms. Significant differences were found between exposed and controls in terms of SCEs frequency (P = 0.001) and replication index value (P = 0.005), but not in terms of CAs (P = 0.201) and aberrant cells (P = 0.227) frequencies. Regression analyses indicated that age and the years of employment did not influence the level of chromosomal damage in both groups. Finally, among anesthetists, GSTT1 null individuals showed a significant higher frequency of SCE with respect to GSTT1-positive subjects.

Impact of glutathione S-transferase T1 gene polymorphisms on acute cellular rejection in living donor liver transplantation

It has previously been demonstrated that glutathione S-transferase T1 (GSTT1) genetic mismatch between recipient and donor is a risk factor for developing immune-mediated hepatitis following liver transplantation and for antibody-mediated rejection in renal transplantation. Little is known whether the GSTT1 gene polymorphism affects the incidence of acute cellular rejection (ACR) following living donor liver transplantation (LDLT). Patients underwent LDLT at Nagoya University or Kyoto University, Japan, between 2004 and 2009. Genotyping of GSTT1 genes (null or present genotype) was conducted in recipients and donors. A total of 155 LDLT cases were examined. Forty-seven recipients (30.3%) developed early ACR. There was no association of recipient GSTT1 genotype with ACR incidence. However, ACR incidence was significantly higher in recipients transplanted from GSTT1 present genotype donors than in those transplanted from GSTT1 null genotype donors [odds ratio (OR)=2.64, 95% confidence interval (CI)=1.12–5.83, p=0.016]. Moreover, GSTT1 recipient/donor genotype mismatch (present/null or null/present) was significantly associated with ACR development (OR=2.28, 95% CI=1.12–4.61, p=0.022). The genotyping of GSTT1 in recipients and donors might be useful to stratify the liver transplant recipients according to risk of ACR.

Relationship Between GSTT1 Gene Polymorphism and Hepatocellular Carcinoma in Patients from China

The results from studies on associations of the glutathione S-transferase T1 (GSTT1) gene polymorphism and hepatocellular carcinoma (HCC) risk in Chinese populations are still conflicting. This meta- analysis was performed to evaluate the relationship in detail. Eligible reports were recruited into this meta-analysis from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Eighteen investigations were identified for the analysis of association between polymorphic deletion of GSTT1 and HCC, consisting of 2,693 patients with HCC and 4,696 controls. Null genotype of GSTT1 was associated with HCC susceptibility in Chinese (OR=1.53, 95%CI: 1.28-1.82; P<0.00001). The GSTT1 null genotype is associated with HCC susceptibility in Chinese.

Lack of association between glutathione S-transferase T1 gene polymorphism and laryngeal cancer susceptibility: A meta-analysis based on 2,124 cases and 2,059 controls

Studies investigating the association between glutathione S-transferase T1 (GSTT1) gene polymorphism and laryngeal cancer susceptibility have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of GSTT1 gene polymorphism with laryngeal cancer risk. The relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge and Chinese National Knowledge Infrastructure until May 2011. Twelve studies were included in the present meta-analysis, which described a total of 2124 laryngeal cancer cases and 2059 controls. The overall odds ratio (OR) for GSTT1 null genotype was 1.40 (95% CI=0.90–2.16). When stratifying for race, the pooled ORs for GSTT1 null genotype were 1.07 (95% CI=0.81–1.41) in Caucasians and 5.63 (95% CI=1.00–31.83) in Asians. The pooled ORs for GSTT1 null genotype were 1.03 (95% CI=0.71–1.49) in population-based studies and 2.39 (95% CI=0.73–7.86) in hospital-based studies, stratifying for study design. This meta-analysis suggested that there was lack of association between GSTT1 gene polymorphism and laryngeal cancer risk. However, larger scale primary studies are still required to further evaluate the interaction of GSTT1 gene polymorphism with laryngeal cancer risk.

GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer

This work investigates the role of glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and glutathione S-transferase P1 (GSTP1) enzymes and polymorphisms, which are found in phase II detoxification reactions in the development of cervical cancer. This study was conducted with 46 patients diagnosed with cervical cancer and 52 people with no cancer history. Multiplex PCR methods were used to evaluate the GSTM1 and GSTT1 gene polymorphism. However, the GSTP1 (Ile105Val) gene polymorphism was studied using a PCR-RFLP method. The patient and control groups were compared using a chi-square test with p<0.05. In the patient group, statistical significance was determined for gravidity (p=0.03), parity (p=0.01), and the number of living children (p=0.01) compared to the control group. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphisms was evaluated. We observed that GSTM1 and GSTT1 null genotype frequencies were 54.3% and 32.6% respectively, while GSTP1 (Ile/Val), (Ile/Ile), (Val/Val) genotype frequencies were 52%, 44%, and 4%, respectively, in the cervical cancer patients. No statistical variation was determined between the control and patient groups in terms of GSTM1, GSTT1, and GSTP1 polymorphisms (p>0.05). Our results demonstrate that GSTT1, GSTM1, and GSTP1 polymorphisms are not associated with cervical cancer in Turkish patients.

Glutathione S-Transferase T1 (GSTT1) Gene Polymorphism and Gastric Cancer Susceptibility: A Meta-Analysis of Epidemiologic Studies

Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and gastric cancer risk have reported conflicting results. Therefore, we conducted this meta-analysis to provide more precise evidence. We searched the databases Medline, PubMed, Embase, and China National Knowledge Infrastructure up to July 30, 2009. Thirty-six studies with 4,357 gastric cancer cases and 9,796 controls were selected. Odds ratio (OR) and 95% confidence intervals (CI) were calculated based on fixed- and random-effects models. The combined results based on all studies showed there was a significant link between GSTT1 null genotype and gastric cancer risk (OR = 1.14, 95%CI = 1.01-1.28). In subgroup analysis stratified on the basis of ethnic group, we also observed positive association between GSTT1 polymorphism and gastric cancer risk among Caucasians (non-Europeans + non-Americans), but not among East Asians. When stratifying by control source, the overall ORs for population- and hospital-based studies were 1.09 (95%CI = 0.94-1.28) and 1.17 (95%CI = 1.03-1.34), respectively. Subjects with both GSTM1 and GSTT1 negative genotypes had increased gastric cancer risk compared with those who had nonnull genotypes of both GST genes. Subgroup analyses for Helicobacter pylori infection and smoking habit did not reveal any significant association between GSTT1 polymorphism and gastric cancer development. This meta-analysis suggests that GSTT1 gene polymorphism may be not associated with increased gastric cancer risk among Europeans, Americans, and East Asians. More large-scale studies based on the same racial group are needed.

Analysis of glutathione S-transferase M1 and glutathione S-transferase T1 gene polymorphisms suggests age-related relationships in a northern Italian population

The present work attempts to determine the distribution of GSTM1 and GSTT1 genotype and allele frequencies in a sample of northern Italian population, and to examine the age-related association of these polymorphisms. The frequencies of the deleted GSTM1 and GSTT1 genotypes were 0.357 and 0.169, respectively. GSTT1 null-genotype frequency found in this work further confirms data obtained in previous studies of Italian populations, while for GSTM1 deletion our sample showed a significantly lower-frequency value with respect to other Italian and European populations, with exception of the Greek. No significant differences occurred between men and women in the frequency of each gene, which could suggest that, in the studied sample, there were no sex differences in susceptibility to diseases and in detoxifying enzymes such as GSTs. In order to analyze the relationship between GSTT1 and GSTM1 gene polymorphisms and age, the sample was subdivided into four age groups: 1-30 years (n = 101); 31-50 years (n = 160); 51-79 years (n = 144) and 80-100 years (n = 58). This age-related analysis showed a decreasing gradient of GSTs null genotypes between younger and older groups, with the 80-100 age group showing a significantly lower frequency of GSTT1 null, GSTM1 null and GSTT1/GSTM1 double null genotypes with respect to the younger group.

Glutathione-S-transferase M1 and T1 Genetic Polymorphisms and the Risk of Cataract Development: A Study in the Turkish Population

In this study, we aimed to determine the effects of genetic polymorphisms of glutathione-S-transferase M1 (GSTM1) and glutathione-S-transferase T1 (GSTT1) on risk of developing different subtypes of age-related cataract in the Turkish population. Using a multiplex polymerase chain reaction (PCR), GSTM1 and GSTT1 gene polymorphisms were analyzed in 195 patients with age-related cataract (75 patients with cortical, 53 with nuclear, 37 with posterior subcapsular, and 30 with mixed type) and in 136 patients of an otherwise healthy control group of similar age. GSTM1 null genotype had a significant association with the development of cataract in female subjects (p < 0.0029; OR, 2.98; 95% CI, 1.41–6.34). This relationship in female subjects was only in nuclear and mixed types cataract cases (p < 0.002; OR, 4.58; 95% CI, 1.67–12.78 and p < 0.03, respectively). There was also a statistically significant association between the combination of GSTM1-null and GSTT1-positive genotypes and the risk of cataract development in female subjects (p = 0.01; OR = 2.87; 95% CI = 1.25–6.69). Stratification by the subtypes revealed that this association was only in nuclear type cataract (p = 0.001; OR, 3.92; 95% CI, 1.34–11.71). GSTM1-null genotype or combination of the GSTM1-null and GSTT1-positive genotypes in females may be associated with increased risk of cataract development in the Turkish population.

Glutathione S-transferase M1 and GST T1 genetic polymorphisms and Raynaud’s phenomenon in French vinyl chloride monomer-exposed workers

Occupational vinyl chloride monomer (VCM) exposure can induce Raynaud's phenomenon (RP). However, not all VCM workers developed RP, which suggests an underlying genetic susceptibility. Genetic polymorphisms of glutathione S-transferases (GSTs), involved in VCM metabolism, have been shown to influence certain VCM-related health effects. We have conducted a case-control study of 58 subjects with RP along with 247 subjects without RP, from a population of 305 French workers exposed or formerly exposed to VCM, to assess any association between GST M1 and GST T1 gene polymorphisms, either separately or in combination, and the presence of RP. None of the GST M1 or GST T1 genotypes were significantly associated with the presence of RP among studied VCM workers. A combination of positive genotypes for both GST M1 and GST T1 was significantly associated with RP presence, compared to the other combinations of genotypes (OR=2.1, 95% CI=1.1-3.8). OR adjusted for age, smoking status, alcohol consumption and history of treated hypertension did not reach significance (OR=2.0, 95% CI=0.9-5.2). None of the GST M1 and GST T1 genotypes seem to contribute separately to the presence of RP, suggesting that they are not, when taken alone, a major determinant of interindividual variability for VCM-induced PR. However, the combination of both positive GST M1 and GST T1 genotypes appears to contribute slightly to susceptibility to RP in VCM-exposed subjects. Nevertheless, our study-the first to examine the role of a genetic component in the occurrence of RP secondary to occupational exposure to a chemical-corroborates the previous considerations that interaction between the genetic constitution and environmental factors is of importance in determining the health-adverse effects of VCM exposure.