Genomic Pattern of GSTM1 and T1 Gene Null polymorphism of Head and Neck Cancer Patients in Eastern India.

OBJECTIVE: Homozygous deletion i.e., null polymorphism of the Glutathione S transferases genes hinders detoxification reactions by altering the sensitization of glutathione s transferases enzymes. Hence, we analysed the association between the GSTM1 and GSTT1 gene polymorphisms and head and neck cancer (HNC). METHODS: The study consists of 238 healthy controls and 160 diagnosed cases of HNC, who attended the Regional Cancer Centre, Indira Gandhi Institute of Medical Sciences (a tertiary care hospital). DNA was extracted from whole blood of patients and control using Qiagen DNA extraction kit. GSTM1 and GSTT1 gene polymorphisms were examined using PCR and agarose gel electrophoresis. RESULTS: GSTM0 null polymorphism was 26.25% and 15.13% in cases and control respectively. GSTT0 null polymorphism was observed in 18.13% cases and 8.82% in control groups. The GSTM0 null polymorphism was present significantly in case group as compared to control group (OR = 1.997, p = 0.006). There was also significant association of GSTT0 null polymorphism with case group as compared to control group (OR = 2.288, p = 0.006). The combined genotypes were also analysed. GSTM0T1 genotype (n = 27) was found to be most common among HNC group followed next by GSTM0T0 double deletion (n =15). CONCLUSION: The result indicated that there was strong association of GSTM0 and GSTT0 null polymorphism in those patients. The combined genotypes i.e., GSTM0T1 and GSTM0T0 null polymorphism also showed significant association in HNC patients.

Frequency of null genotypes of glutathione S-transferase M1 and T1 in Japanese patients with drug-induced liver injury.

AIM: Previous reports suggest that the null genotype (*0/*0) of glutathione S-transferase (GST) M1 and/or GSTT1 could be risk factors for drug-induced liver injury (DILI). However, multi-institutional pharmacogenetic research with various suspected drugs has rarely been performed in Japan. Therefore, the aim of this study was to investigate the role of GSTM1 and GSTT1 null genotype in the occurrence of DILI in Japanese patients. METHODS: Blood samples of 270 DILI patients from 23 hospitals throughout Japan collected between 2010 and 2018 were subjected to genotyping of null genotypes of GSTM1 and GSTT1 using the SmartAmp-2 method. We also collected information on DILI types, time to onset of DILI, pharmacological classification of suspected drugs and Digestive Disease Week-Japan score, as well as genotypes of GSTM1 and GSTT1 in each patient with DILI. RESULTS: The distribution of a combination of null genotypes of GSTM1 and GSTT1 in Japanese patients with DILI was significantly different from that reported in the general Japanese population. Notably, the incidence of the GSTM1 null genotype in patients with DILI was significantly higher than that of the control population. A significant relationship between the frequency of GSTM1 and GSTT1 null genotypes and pharmacological classification of suspected drugs, clinical laboratory data for liver function, time to onset of DILI, and Digestive Disease Week-Japan scores was not observed. CONCLUSIONS: The GSTM1 null genotype was associated with an increased incidence of DILI in Japanese patients.

Avaliação dos níveis da citocina pró-inflamatória fator de necrose tumoral-α em pacientes com diabetes tipo 2 e sua relação com variações genéticas de enzimas antioxidantes e obesidade / Evaluation of proinflammatory cytokine tumor necrosis factor-α levels in obese vs nonobese patients with type 2 diabetes and their relationship to CAT C-262T polymorphism

Introdução: Diabetes tipo 2 (DM2) é um distúrbio multifatorial caracterizado pelo aumento dos níveis de radicais livres. Tanto o estresse oxidativo quanto a obesidade contribuem para um estado inflamatório da doença, principalmente pelo aumento da citocina TNF-α. Sabendo-se que a genética individual pode contribuir para o estresse oxidativo, o estudo avaliou o impacto das variações genéticas de enzimas antioxidantes C262T no gene CAT e polimorfismos nulos dos genes GSTM1 e GSTT1 nos níveis de TNF-α, assim como, avaliou se as variantes genéticas atuariam sinergicamente com a obesidade aumentando os níveis da citocina em diabéticos da Grande Vitória/ES, Brasil.Métodos: O polimorfismo no gene CAT foi avaliado pela técnica PCR/RFLP e nos genes GSTM1 e GSTT1 por PCR multiplex, em 56 pacientes, sendo 28 obesos e 28 não obesos. Níveis de TNF-α foram medidos pela técnica de ELISA sanduíche.Resultados: Frequências das variantes nulas de GSTM1 e GSTT1 foram 44,6% e 17,9%, respectivamente. As frequências genotípicas C262T-CAT foram 73,2%, 25% e 1,8% para homozigoto normal, heterozigoto e homozigoto polimórfico, respectivamente. Não houve associação entre genótipos polimórficos e aumento dos níveis de TNF-α, assim como, não foi demonstrado aumento significante da citocina quando avaliado o sinergismo entre obesidade e genética individual do paciente.Conclusão: Níveis de TNF-α não se elevam em diabéticos tipo 2 na presença dos polimorfismos nos genes CAT, GSTM1 e GSTT1, e a obesidade não atua no aumento dessa citocina na população estudada, separadamente ou em conjunto com a genética individual de variantes nos genes CAT, GSTM1 e GSTT1.

Introduction: Type 2 diabetes is a multifactorial disorder characterized by increased levels of free radicals. Both oxidative stress and obesity contribute to an inflammatory state of the disease, mainly by increasing the levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). Considering that personal genetics may contribute to oxidative stress, this study assessed the impact of CAT C-262T polymorphism and GSTM1 and GSTT1 null polymorphisms on TNF-α levels in patients with type 2. diabetes. The study also evaluated whether the genetic variants act synergistically with obesity to increase TNF-α levels in patients with diabetes from Grande Vitória, Brazil.Methods: Fifty-six patients were included, of whom 28 were obese and 28 were nonobese. The CAT gene polymorphism was assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, whereas GSTM1 and GSTT1 polymorphisms were assessed using multiplex PCR. TNF-α levels were measured using the sandwich ELISA technique.Results: Frequencies of GSTM1 and GSTT1 null polymorphisms were 44.6% and 17.9%, respectively. The genotype frequencies of CATC-262T polymorphism were 73.2%, 25.0%, and 1.8% for normal homozygote, heterozygote, and polymorphic homozygote, respectively. Polymorphic genotypes were not associated with increased TNF-α levels, and there was no significant increase in TNF-α levels when evaluating the synergism between obesity and personal genetics.Conclusion: The presence of CAT, GSTM1, and GSTT1 gene polymorphisms was not associated with increased TNF-α levels in patients with type 2 diabetes. Obesity alone or combined with personal genetics of CAT, GSTM1, and GSTT1gene polymorphisms did not promote increased TNF-α levels in the study population.

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.

Modifying Effect of Smoking on GSTM1 and NAT2 in Relation to the Risk of Bladder Cancer in Mongolian Population: A Case-Control Study.

OBJECTIVES: Tobacco smoking is the predominant risk factor for bladder cancer as it contains cancer-causing chemicals. However, genetic factors may play important role in response towards chemical carcinogens. In this study we aim to investigate genetic polymorphisms of glutathione S-transferase M1 (GSTM1) and N-acetyltransferase 2 (NAT2) as determinants of bladder cancer risk, independently and in combination with tobacco use in the Mongolian population. MATERIALS AND METHODS: The current study was a hospital-based case-control study including 60 histologically confirmed bladder cancer patients and 60 cancer-free controls. PCR-RFLP assay was used to determine the presence of GSTM1 and NAT2 polymorphisms in bladder cancer patients and controls. GSTM1 and NAT2 were tested using binary logistical regression analysis with adjustment or stratification according to the smoking. RESULTS: There were 46 men and 14 women diagnosed with bladder cancer, with mean age was 58±4. The controls included 37 men and 23 women with a mean age of 57±3. The frequency of GSTM1 null genotype was higher in controls (71.67%) than in bladder cancer patients (58.33%) without statistical significance (OR=0.5534; 95% CI=0.2586-1.1843), (p=0.128). The NAT2 low acetylator phenotype was more common in patients with bladder cancer (15%) than in controls (5%). Furthermore, individuals with NAT2 low acetylator phenotype had a nearly 3.35-fold increased risk to develop bladder cancer (OR=3.35; 95% CI=0.8604-13.0657), (p=0.081) while the risk was even higher when combined with null GSTM1 genotype (OR=4; 95% CI=0.4459-37.5308), (p=0.213) but there was no statistical significance. Prevalence of smoking in bladder cancer patients was higher than controls and increased significantly the risk of bladder cancer (OR=8.31; 95% CI=3.66-18.88). Smokers with GSTM1 null genotype were at 5-fold higher risk of bladder cancer (OR=5.0; 95% CI=1.55-16.16), (p=0.007) while NAT2 low acetylator phenotype increased bladder cancer risk by 20-fold (OR=20.5; 95% CI=2.33-80.86), (p=0.006). CONCLUSION: The current study shows that tobacco smokers with the NAT2 low acetylator phenotype and GSTM1 null genotype have the highest risk of bladder cancer in the Mongolian population.
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Genetic Variation of Glutathione S-Transferase M1 Is Associated with Patients with Ovarian Endometriosis and Endometriosis-Related Primary Infertility.

BACKGROUND: The aim of the study was to investigate the role of the genetic variation of glutathione S-transferase M1 (GSTM1) in the development of ovarian endometriosis and endometriosis-related primary infertility risk. METHODS: This case-control study included 564 women with ovarian endometriosis and 576 normal women in the control group in northern China. The polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR)/ligase detection reaction method. To assess the biological significance of polymorphisms, the level of GSTM1 mRNA expression in patients' endometrial tissues with different genotypes was detected by quantitative real-time PCR (qRT-PCR). RESULTS: Compared with the positive genotype, the null genotype of GSTM1 was associated with the risk of developing ovarian endometriosis (OR = 1.29, 95% CI = 1.02-1.62). Further analysis showed that patients with a null genotype also had a significantly higher risk of primary infertility than patients with positive genotypes (OR = 1.59, 95% CI = 1.01-2.49). In addition, we found that GSTM1 mRNA expression was present in the endometrial tissue of all patients, but the expression level of patients with a positive genotype was nearly 10 times higher than that of patients with a negative genotype. CONCLUSION: Our results suggest that the GSTM1 polymorphism is not only related to the genetic susceptibility to ovarian endometriosis but also a potential molecular marker of primary infertility in patients with ovarian endometriosis.

Effects of glutathione S-transferase M1 and T1 deletions on Parkinson's disease risk among a North African population.

PURPOSE: In this study, the effects of glutathione S-transferase polymorphisms Mu1 (GSTM1) and glutathione S-transferase polymorphisms Theta1 (GSTT1) on Parkinson's disease (PD) risk factor were evaluated in a Tunisian population. METHODS: These polymorphisms were analyzed in 229 healthy Tunisian subjects and 64 Tunisian patients with PD, using a polymerase chain reaction (PCR). Statistical analysis was performed using SPSS 18.0. The relative associations between the GST genotypes and PD were assessed by calculating the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The study results demonstrated that the individuals with GSTM1 [OR=3.93, 95% CI: 1.98-7.92, P=10-6] and GSTT1 [OR=5.45, 95% CI: 2.90-10.30, p=10-6] were statistically associated with the risk of PD. A significant association was also found between the individuals with both GSTM1/T1 null genotypes and PD risk [OR=22.10, 95% CI: 6.99-73.75, P=10-6]. CONCLUSION: These genotyping findings suggest that the absence of both GSTM1 and GSTT1 activity could be a contributory factor for the development of PD.

Frequency and Association Of GSTM1 and GSTT1 Gene Polymorphisms with Survival in Breast Cancer Patients.

OBJECTIVE: Glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) are the key detoxification enzymes of xenobiotics, including chemotherapeutic drugs. The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that influenced clinical outcomes of chemotherapeutic agents in breast cancer. However, there is limited information among Thai patients. This research aims to explore the frequency and role of GSTM1 and GSTT1 polymorphisms on survival among Thai patients with breast cancer. METHODS: The retrospective cohort study was performed. Demographic data and clinicopathology characteristics were collected from hospital base registry data and medical records. A multiplex qualitative real-time PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 gene in the genomic DNA samples of the participants. RESULTS: The frequencies of the GSTM1 and GSTT1 null genotypes in 198 breast cancer patients were 65.70% and 33.30%, respectively. The overall survival at 1, 3 and 5 years were 95.00%, 83.00%, 71.00% respectively. The log rank test and Cox proportional hazards revealed a significant different in the 5-years overall survival according to lymph node metastasis and tumor stage (P = 0.014 and P < 0.001). No associations between overall survival and GSTM1 or GSTT1 genotype were found in single or combined genotypes analyses (P = 0.76 and P= 0.15). CONCLUSION: The results of our study provided the epidemiological information for prognostic of survival in breast cancer patients treated with chemotherapy.
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Lack of association between glutathione S-transferase M1 and T1 gene polymorphisms and susceptibility to preeclampsia: An updated systematic review and meta-analysis.

Insufficient response to oxidative stress in placenta is proposed as a contributing factor for preeclampsia (PE) development. Glutathione S-transferases (GST) have significant role in detoxification processes. Conflicting results were published by several research groups regarding GST T1 and GST M1 deletion polymorphism as risk factors for PE. The aim of the present meta-analysis was to get a better understanding of the impact of these polymorphisms in preeclampsia development. To identify relevant case-control studies, the author team searched Clarivate Analytics Web of Science, Scopus, PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, major subject journals, and gray literature. Pooled odds ratios and 95% confidence intervals for GST M1 and GST T1 deletion polymorphism and preeclampsia were derived from random effects models. This meta-analysis included 10 eligible studies. The pooled analyses showed no association between GST M1/GST T1 deletion polymorphisms and susceptibility to PE. Even though high heterogeneity was founded among results for GST M1 and double null genotypes, Egger's and Begg's tests (0.17 and 0.18, respectively) revealed no statistical evidence of publication bias among included studies. The present updated systematic review and meta-analysis found no association between GST M1 and GST T1 deletion polymorphism and PE risk.

Polymorphism of glutathione S-transferase in the population of Polish patients with carcinoma of the prostate.

The aim of the study was frequency analysis of GSTM1, GSTT1, and GSTP1 polymorphisms of glutathione S-transferase in the group of patients with prostate cancer and in a control group of healthy individuals. Genomic DNA was isolated; molecular analysis of glutathione S-transferase M1 and T2 polymorphisms was performed using multiplex PCR and RFLP methods. The products of the PCR reaction were then visualized in agarose gel, and a statistical analysis of the results was performed. No statistically significant differences were found in the frequency of glutathione S-transferase polymorphisms between 66 patients with prostate cancer and the control group (64 healthy volunteers). The GSTM1 gene deletion was found in ca. 47% of patients with prostate cancer and in ca. 55% of the controls. The GSTT1 deletion was found in approximately 17% of patients and 14% of the controls. The distribution of GSTP1 Ile/Ile, Ile/Val, and Val/Val polymorphisms was ca. 51.5%, 39%, and 9% in the group of patients and 61%, 34%, and 5% in the control group, respectively. The results indicate that there is no relationship between glutathione S-transferase polymorphisms and prostate cancer in the study group, which is a novelty when compared with the previous work on the role of these genetic variants in the etiology of cancer.

GSTM1 and Liver Iron Content in Children with Sickle Cell Anemia and Iron Overload.

Chronic blood transfusions in patients with sickle cell anemia (SCA) cause iron overload, which occurs with a degree of interpatient variability in serum ferritin and liver iron content (LIC). Reasons for this variability are unclear and may be influenced by genes that regulate iron metabolism. We evaluated the association of the copy number of the glutathione S-transferase M1 (GSTM1) gene and degree of iron overload among patients with SCA. We compared LIC in 38 children with SCA and ≥12 lifetime erythrocyte transfusions stratified by GSTM1 genotype. Baseline LIC was measured using magnetic resonance imaging (MRI), R2*MRI within 3 months prior to, and again after, starting iron unloading therapy. After controlling for weight-corrected transfusion burden (mL/kg) and splenectomy, mean pre-chelation LIC (mg/g dry liver dry weight) was similar in all groups: GSTM1 wild-type (WT) (11.45, SD±6.8), heterozygous (8.2, SD±4.52), and homozygous GSTM1 deletion (GSTM1-null; 7.8, SD±6.9, p = 0.09). However, after >12 months of chelation, GSTM1-null genotype subjects had the least decrease in LIC compared to non-null genotype subjects (mean LIC change for GSTM1-null = 0.1 (SD±3.3); versus -0.3 (SD±3.0) and -1.9 (SD±4.9) mg/g liver dry weight for heterozygous and WT, respectively, p = 0.047). GSTM1 homozygous deletion may prevent effective chelation in children with SCA and iron overload.

Association of Glutathione-S-Transferases M1 and T1 Deletional Variants with Development of Oral Squamous Cell Carcinoma: A Study in the South-East of Iran.

Background: The role of genetic polymorphisms in genes of Glutathione-S-transferases (GST) enzymes in susceptibility to oral cavity cancers is controversial. Oral Squamous Cell Carcinoma (OSCC) is the most common oral cavity neoplasm. Aimed to evaluate the potential impacts of two well-known null variants residing in the gene encoding GSTM1 and GSTT1 enzymes of OSCC patients in the southeast of Iran. Methods: In a case-control design, 113 individuals (50 OSCC patients, and 63 healthy subjects) were included. DNA was extracted using paraffin-embedded tissues. GST genotyping was carried out using multiplex PCR. Results: In 113 participants, 41 (36.3%) and 72 (63.7%) were males and females respectively. No significant difference was recognized for distribution of GSTM1 (P=0.11) and GSTT1 (P=0.28) null genotypes between OSCC patients (58%, and 24% respectively) and healthy controls (42.9% and 15.9% respectively). Also, no significant difference was noted regarding the frequency of GSTM1 null genotype in different histological grades, however, those patients with more aggressive disease (poorly differentiated or grade III) revealed with a significantly higher ratio (66.7%) of GSTT1 null genotype (P=0.002). The highest odds ratio for OSCC was related to combined null genotypes for GSTM1 and GSTT1 (OR=2.5, 95% CI: 0.7-9.2), however, this was not statistically significant finding (P=0.15). Conclusion: Null genotypes polymorphisms were more common in OSCC than healthy individuals. GSTT1 null genotype may be an important genetic factor in the progression of OSCC.

GSTM1 and GSTT1 copy number variants and the risk to Thai females of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy found throughout the world that most often occurs in males. The cancer is associated with many risk factors such as viral infection, cirrhosis, alcohol, smoking, and fungal toxins. GSTM1 and GSTT1 are detoxification enzymes activated by the cleansing of carcinogenic compounds. Low DNA copy numbers of Glutathione S-transferases M1 and T1 result in a loss of enzyme activity, which causes carcinogenesis factors. DNA copy number variants (CNVs) were determined to compare the differences between the frequencies of GSTM1 and GSTT1 in a control group and patients. Then, the association of these genes with the pathological/survival status of HCC patients was investigated. METHODS: Forty-nine Thai HCC patients' DNA and the genomic DNA of 66 healthy controls were investigated for GSTM1 and GSTT1 CNVs by real-time polymerase chain reaction (PCR). Then, the correlations between GSTM1 and GSTT1 patients' CNVs, the control group, and clinico-pathological parameters were determined. RESULTS: The results show that were no differences between the CNVs of GSTM1 and GSTT1 in the controls and patients (P≥0.05). Only GSTT1 genotypes 0/0 correlated to an increase in the risk of hepatocellular carcinogenesis (OR value was 1.88). GSTM1 CNVs were associated with the gender of patients (P=0.002). However, no correlations were found between GSTT1 CNVs and any of the clinico-pathological parameters. CONCLUSIONS: The results suggest that only GSTT1 CNVs are associated with increased risk factors of HCC in Thais. GSTM1 copy numbers had a dominant correlation with female HCC patients.

Glutathione-S-transferase M1 polymorphism and pro-inflammatory cytokines tumour necrosis factor-α and interleukin-1ß are associated with preeclampsia in Serbian women.

PROBLEM: Preeclampsia has a multifactorial origin with genetic, immunological, and environmental factors described as main contributors to its onset. This study aimed to investigate glutathione-S-transferase M1 (GSTM1) and glutathione-S-transferase T1 (GSTT1) gene polymorphisms, the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6), and the potential relationship between GST polymorphisms and cytokine expression levels in preeclampsia and uncomplicated pregnancy. METHOD OF STUDY: This prospective case-control study included 50 women with preeclampsia and 50 healthy pregnant women. DNA and RNA were extracted from women leukocytes. Deletion polymorphisms were analyzed by PCR, while cytokine mRNA expression was analyzed by real-time PCR. RESULTS: GSTM1 null genotype with present GSTT1 increased the risk for preeclampsia development. Deletion of GSTT1 without deletion of GSTM1 increased the risk for early preeclampsia. Relative mRNA expression of TNF-α was significantly higher in preeclampsia compared to healthy pregnant women (P = 0.006). Expression of IL-1ß was significantly higher in severe and late preeclampsia compared to the control group (P = 0.005, P = 0.007, respectively). A significant positive correlation between TNF-α and IL-1ß was observed (Spearman's ρ = 0.312, P = 0.028) and between IL-1ß and IL-6, in preeclampsia group (Spearman's ρ = 0.296, P = 0.037). IL-1ß was significantly increased in patients with GSTT1 null genotype (P = 0.015) while IL-6 was increased in patients with GSTM1 null genotype (P = 0.015). CONCLUSIONS: GSTM1 null genotype represents a risk factor for preeclampsia development, while GSTT1 null genotype favors early preeclampsia. Preeclampsia is also associated with increased expression of pro-inflammatory cytokines, predominantly TNF-α and IL-1ß.

The influence of GSTT/GSTM null genotypes in scarring.

BACKGROUND AND AIMS: The process of scarring is a common denominator of interest for the medical field. From general medicine to dentistry, pathological scar tissue represents a challenge in providing optimal care to a patient. The present study aims to investigate whether a systemically reduced antioxidant potential, revealed by null isoforms of glutathione S transferase, affects the process of scarring in a group of female patients. METHODS: The study is based on a group of 54 patients with physiological scars after a 6-month observation period, as well as 18 patients with hypertrophic or atrophic scars. Peripheral venous blood was collected, from which DNA was extracted using a commercial kit. Genotyping followed a Multiplex PCR protocol for GSTT1/GSTM1. RESULTS: In a dominant model, the combination of wild type (heterozygous or homozygous) GSTT1 and GSTM1 was negatively associated with pathological scarring, with the wild type (heterozygous or homozygous) GSTM1 genotype being potentially responsible for this effect. Other factors affecting pathological scarring were investigated: family history, phototype, as well as scores on the POSAS and SCAR scales. CONCLUSIONS: The presence of GSTT1 and GSTM1 alleles brings forward an increased antioxidant capacity, serving as a protective factor for patients during scar formation.

Glutathione S-transferase M1 and T1 null genotypes and bladder cancer risk: A meta-analysis in a single ethnic group.

AIM OF STUDY: To further evaluate the influence of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null genotypes on bladder cancer risk, we conducted a meta-analysis in the Chinese population. MATERIALS AND METHODS: PubMed and Chinese databases were electronically searched through April 2016. RESULTS: Nine studies were included for our meta-analysis, involving 1646 bladder cancer cases and 1938 controls. In general, our findings indicated that a significant association existed between GSTM1-null genotype and the risk of bladder cancer in the studied Chinese population (odds ratio = 1.56, 95% confidence interval: 1.36-1.79). However, no significant association between GSTT1 polymorphism and bladder cancer was found. After stratification of the subgroup analyses by source of controls and geographical areas, a substantially elevated risk was revealed between GSTM1-null genotype and bladder cancer in the population-based studies and those conducted in South China and North China. CONCLUSION: Our meta-analysis suggested that GSTM1-null genotype is associated with an increased bladder cancer risk in the Chinese individuals.

Glutathione S-transferase M1 and T1 polymorphisms and the risk of mild hepatotoxicity induced by carbamazepine in a tunisian population study.

BACKGROUND: The aim of this study was to evaluate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null alleles may contribute to carbamazepine-induced hepatotoxicity. METHODS: A cross-sectional prospective study was conducted to identify the frequency distribution of GSTM1 and GSTT1 alleles in 129 Tunisian epileptic patients treated with carbamazepine. Null alleles were determined using a Polymerase Chain Reaction. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by standard methods. RESULTS: Our results showed that the frequencies of GSTM1 (-) null allele and GSTT1 null (-) allele were 74.4 and 17.8% respectively. The ALT and AST levels were elevated in 46 (35.7%) and 33 (25.6%) cases. The mean values of ALT and AST were approximately 1.32 and 3.61 times higher than the upper limit of normal levels, respectively. The values of ALT and AST were significantly higher in GSTM1 (-) allele than in GSTM1 (+) (p = 10-3.and 0.004, respectively). The level of ALT was significantly higher in combination of GSTM1 (-)/T1(-) than in combined GSTM1(-)/T1(+) and combined GSTM1(+)/T1(+) (p = 0.2 and 0.03, respectively), and that of AST was significantly higher in combination of GSTM1(-)/T1(-) and in combination of GSTM1(+)/T1(-) than in combination of GSTM1(+)/T1(+) (p = 10-3 and 10-3, respectively). CONCLUSIONS: Our findings suggest that the GSTM1 (-) allele may be considered as a key factor for the development of carbamazepine-induced hepatotoxicity. Results related to GSTT (-) allele and elevation in AST levels should be considered with caution as AST may be elevated in other pathophysiological conditions.

Association of glutathione S-transferase M1 polymorphisms in the colorectal cancer risk: A meta-analysis.

PURPOSE: The glutathione S-transferase M1 (GSTM1) as a member of phase II detoxification enzymes is expressed in many tissues and plays a critical role in preventing the occurrence of cancer. Published data regarding the associations between the GSTM1 polymorphism and colorectal cancer (CRC) risk are inconclusive. MATERIALS AND METHODS: A meta-analysis of 55 case-control studies involving 17,498 cases and 26,441 controls were performed to assess the strength of association using odds ratio (OR) with 95% confidence interval (CI). RESULTS: The meta-analysis of those studies suggested that GSTM1 null genotype was significantly associated with CRC risk (OR = 1.13, 95% CI = 1.06-1.20, P < 0.0001). In the subgroup analysis by ethnicity, significant risks were associated with GSTM1 null genotype in Caucasians (OR = 1.18, 95% CI = 1.07-1.29, P = 0.001), Asians (OR = 1.11, 95% CI = 1.02-1.22, P = 0.02), and mixed group (OR = 1.01, 95% CI = 0.90-1.14, P = 0.85). In the subgroup analysis by study design, significant elevated risks were associated with GSTM1 null genotype in hospital-based case-control study group (OR = 1.20, 95% CI = 1.10-1.31, and P < 0.0001) but not in population-based case-control study group (OR = 1.03, 95% CI = 0.96-1.10, P = 0.43). CONCLUSIONS: Based on our meta-analysis, the GSTM1 null genotype is a risk factor for CRC.

Genetic polymorphisms of the CYP1A1, GSTM1, and GSTT1 enzymes and their influence on cardiovascular risk and lipid profile in people who live near a natural gas plant.

The aim of this cross-sectional study was to see whether genetic polymorphisms of the enzymes CYP1A1, GSTM1, and GSTT1 are associated with higher risk of coronary artery disease (CAD) and whether they affect lipid profile in 252 subjects living near a natural gas plant, who are likely to be exposed to polycyclic aromatic hydrocarbons (PAHs). Fasting serum concentrations of biochemical parameters were determined with standard methods. Genetic polymorphisms of CYP 1A1 rs4646903, rs1048943, rs4986883, and rs1799814 were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL), while GSTM1 and GSTT1 deletions were detected with multiplex PCR. Cardiovascular risk was assessed with Framingham risk score, and the subjects divided in two groups: >10% risk and ≤10% risk. The two groups did not differ in the genotype frequencies. MANCOVA analysis, which included lipid parameters, glucose, and BMI with sex, age, hypertension and smoking status as covariates, showed a significant difference between the GSTT1*0 and GSTT1*1 allele carriers (p=0.001). UNIANCOVA with same covariates showed that total cholesterol and triglyceride levels were significantly higher in GSTT1*1 allele carriers than in GSTT1*0 carriers (p<0.001 and p=0.006, respectively). Our findings suggest that CYP1A1, GSTM1, and GSTT1 polymorphisms are not associated with the higher risk of CAD, but that GSTT1 affects lipid profile.

Effects of glutathione S-transferase M1 andT1 deletions on bipolar disorder risk among a Tunisian population.

Glutathione S-transferases (GSTs) enzymes are involved in the detoxification of several endogenous and exogenous substances. In this study, we evaluated the effects of two glutathione S-transferase polymorphisms, (GSTM1 and GSTT1) on bipolar disorder (BPD) risk susceptibility in a Tunisian population. These polymorphisms were analyzed in 229 healthy subjects and 109 patients with BPD, using a polymerase chain reaction. Statistical analysis was performed using SPSS 18.0. The relative associations between the GSTs genotypes and BPD were assessed by calculating odds ratios (ORs) and 95% confidence intervals (CLs). The study results demonstrated that individuals with GSTM1 [OR=1.51, 95% CI: 0.93-2.45, p=0.081] or GSTT1 [OR=1.65, 95% CI: 0.95-2.88, p=0.060] were not associated with the risk of BPD, whereas a significant association was found between individuals with both GSTM1/T1 null genotype and BPD risk [OR=2.96, 95% CI (1.26-7.03), p=0.005]. These genotyping finding revealed that the absence of both GSTM1 and GSTT1 activity could be a contributor factor for the development of BPD.