Search

Abstract Oxidative stress (OS) is believed to be a significant factor in the decline of semen quality, with mitochondrial DNA copy number (mtDNAcn) serving as a sensitive biomarker for both semen quality and mitochondrial dysfunction resulting from oxidative stress. While glutathione S-transferases (GSTs) are commonly known as ‘antioxidant’ enzymes, there is ongoing debate regarding the relationship between GST genotypes and semen quality. In a study involving 568 male volunteers from the outpatient department of Puyang Reproductive Medicine Center, sperm mtDNAcn, semen quality, and GSTM1/GSTT1 genotypes were analyzed to investigate the potential link between GSTM1/GSTT1 gene variations and semen quality, as well as the impact of GSTs gene variations on the connection between sperm mtDNAcn and semen quality. Adjusting for variables such as age, BMI, smoking, and alcohol consumption, it was found that mtDNAcn was significantly correlated with decreased sperm concentration and total sperm count (b = − 0.109, − 0.128, respectively; P = 0.002, 0.001, respectively). GSTM1 was associated with progressive motility (OR 0.390, 95% CI 0.218, 0.697), Straight line velocity (VSL) (OR = 0.606, 95% CI 0.385, 0.953), and Straightness (STR) (OR 0.604, 95% CI 0.367, 0.994), while GSTT1 was linked to progressive motility (OR 0.554, 95% CI 0.324, 0.944) and Beat crossover frequency (OR 0.624, 95% CI 0.397, 0.982). The GSTT1 was found to moderate the relationship between mtDNAcn and sperm motility parameters linearity (LIN), STR, and Wobble (WOB), with additive interaction effects observed between GSTT1 and mtDNAcn on LIN, STR, and WOB (P for interaction = 0.008, 0.034, 0.010, respectively). Overall, this study suggests that GSTT1 and GSTM1 gene variations may play a role in sperm motility, with GSTT1 potentially influencing the impact of oxidative stress on sperm motility.

Background: Glutathione S‐transferases (GSTs) play a significant role in carcinogen detoxification, and hence, polymorphisms of this gene may lead to lung cancer susceptibility. Accordingly, this study is aimed at investigating GSTM1 and GSTT1 polymorphisms' association with lung cancer risk and their effects on the toxicities of platinum‐based chemotherapy used to treat Bangladeshi lung cancer patients. Methods: The study subjects comprised 180 lung cancer patients and 200 healthy volunteers. Genetic polymorphisms of GSTM1 and GSTT1 were analyzed using a multiplex PCR–based method. Chemotherapy toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Results: GSTM1 null genotype was found to be significantly associated with a 1.6‐fold increased risk of lung cancer (OR = 1.60, 95%CI = 1.01–2.52, p = 0.0491), whereas no significant association was observed with GSTT1 null genotype and combined GSTM1 and GSTT1 null genotype. Moreover, no significant relationship was observed between GSTM1 and GSTT1 polymorphisms and the increased risk of platinum‐based chemotherapy‐induced toxicities in lung cancer patients. Conclusions: These findings indicated that the GSTM1 null but not GSTT1 null genotype was significantly associated with lung cancer susceptibility. These polymorphisms were not related to platinum‐based chemotherapy‐induced toxicities in Bangladeshi lung cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: Cisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatininduced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI). Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione S-transferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear. Methods: To investigate the roles of GSTM1 and GSTT1 in cisplatin-induced AKI, we generated GSTM1 and GSTT1 knockout mice using CRISPR-Cas9 technology and assessed their kidney function under normal physiological conditions and cisplatin treatment. Using ELISA kits, we measured the levels of oxidative DNA and protein damage, along with MDA, SOD, GSH, and the GSH/GSSG ratio in wild-type and GSTM1/GSTT1 knockout mice following cisplatin treatment. Additionally, oxidative stress levels and the expression of ferroptosis-related proteins in kidney tissues were examined through Western blotting, qPCR, immunohistochemistry, and immunofluorescence techniques. Results: Here, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatin-treated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin. Discussion: Our study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Cisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatininduced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI). Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione S-transferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear. Methods: To investigate the roles of GSTM1 and GSTT1 in cisplatin-induced AKI, we generated GSTM1 and GSTT1 knockout mice using CRISPR-Cas9 technology and assessed their kidney function under normal physiological conditions and cisplatin treatment. Using ELISA kits, we measured the levels of oxidative DNA and protein damage, along with MDA, SOD, GSH, and the GSH/GSSG ratio in wild-type and GSTM1/GSTT1 knockout mice following cisplatin treatment. Additionally, oxidative stress levels and the expression of ferroptosis-related proteins in kidney tissues were examined through Western blotting, qPCR, immunohistochemistry, and immunofluorescence techniques. Results: Here, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatin-treated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin. Discussion: Our study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases in the world causing painful and swollen joints. RA is a progressive disease that can lead to various physical disabilities. The current study aimed to assess the association of the presence/absence of GSTM1, GSTT1 and single nucleotide polymorphism [SNP] (rs1695) in GSTP1 gene with RA. A cross-sectional study was conducted at Institute of Zoology, Bahauddin Zakariya University Multan from May 2020 to March 2021 and included RA patients (cases; N = 100) and controls (N = 100) enrolled from Multan district in Pakistan. A T-ARMS PCR protocol was applied to report the genotype at studied GSTs. The association of rs1695 in GSTP1 with RA was studied either individually or in various combinations with GATM1 and T1. A significant association of absence of GSTT1 and heterozygous genotype (AG) at rs1695 in GSTP1 was found to be associated with RA in the present study. Subjects whose age varied between 41 and 55 years and women suffered more from RA. It is concluded that polymorphisms in GSTs may disturb the protection provided by them against oxidative stress which may influence disease progression in RA. [ABSTRACT FROM AUTHOR]

Abstract Glutathione S-transferase theta 1 (GSTT1) enzyme plays a key role in the neutralization of electrophilic compounds such as carcinogens. Herein, we aimed to evaluate GSTT1 deletion polymorphism and susceptibility to head and neck carcinoma (HNC) according to 107 articles in a systematic review with five analyses. The databases of PubMed/Medline, Web of Science, Scopus, and Cochrane Library from the beginning of each database until June 21, 2023, with no restrictions to identify pertinent articles. The RevMan 5.3 software was used to calculate the effect sizes, which were displayed as the odds ratio (OR) along with a 95% confidence interval (CI). Both the publication bias and sensitivity analyses were performed using the CMA 3.0 software. A trial sequential analysis (TSA) was conducted. Of the 1966 records retrieved from four databases, 107 articles were included in the analysis. The combined analysis revealed that the pooled OR was 1.28 (95% CI: 1.14 to 1.44; p-value

Glutathione S-transferase theta 1 (GSTT1) enzyme plays a key role in the neutralization of electrophilic compounds such as carcinogens. Herein, we aimed to evaluate GSTT1 deletion polymorphism and susceptibility to head and neck carcinoma (HNC) according to 107 articles in a systematic review with five analyses. The databases of PubMed/Medline, Web of Science, Scopus, and Cochrane Library from the beginning of each database until June 21, 2023, with no restrictions to identify pertinent articles. The RevMan 5.3 software was used to calculate the effect sizes, which were displayed as the odds ratio (OR) along with a 95% confidence interval (CI). Both the publication bias and sensitivity analyses were performed using the CMA 3.0 software. A trial sequential analysis (TSA) was conducted. Of the 1966 records retrieved from four databases, 107 articles were included in the analysis. The combined analysis revealed that the pooled OR was 1.28 (95% CI: 1.14 to 1.44; p-value < 0.0001). The pooled OR was highest in mixed ethnicity. Nasopharyngeal cancer had the highest OR (1.84), followed by oral cancer (OR = 1.20), and laryngeal cancer (OR = 1.17). Studies with less than 200 samples had a higher OR compared to those with 200 or more samples. The studies with a quality score of 7 or more had a higher OR compared to those with a score of less than 7. When both age and sex are considered, while the OR of 1.42 is significant, the high heterogeneity suggests caution in interpreting these results. There is no evidence of publication bias. TSA reported that the study does not have sufficient statistical power. This comprehensive meta-analysis revealed a significant association between the GSTT1 null genotype and an increased risk of HNC, with variations based on factors such as ethnicity, cancer type, sample size, control source, and quality score. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The disease can occur in two clinical forms: dry (the progression is slow and gentle) and exudative (wet—progression is acute and severe), which usually starts in the dry form; however, the coexistence of both forms is possible. The etiology of AMD is not fully understood, and the precise mechanisms of the development of this illness are still unknown. Extensive genetic studies have shown that AMD is a multi-factorial disease and that genetic determinants, along with external and internal environmental and metabolic-functional factors, are important risk factors. This article reviews the role of glutathione (GSH) enzymes engaged in maintaining the reduced form and polymorphism in glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase mu-1 (GSTM1) in the development of AMD. We only chose papers that confirmed the influence of the parameters on the development of AMD. Because GSH is the most important antioxidant in the eye, it is important to know the influence of the enzymes and genetic background to ensure an optimal level of glutathione concentration. Numerous studies have been conducted on how the glutathione system works till today. This paper presents the current state of knowledge about the changes in GSH, GST, GR, and GPx in AMD. GST studies clearly show increased activity in ill people, but for GPx, the results relating to activity are not so clear. Depending on the research, the results also suggest higher and lower GPx activity in patients with AMD. The analysis of polymorphisms in GST genes confirmed that mutations lead to weaker antioxidant barriers and may contribute to the development of AMD; unfortunately, a meta-analysis and some research did not confirm that connection. Unspecific results of many of the parameters that make up the glutathione system show many unknowns. It is so important to conduct further research to understand the exact mechanism of defense functions of glutathione against oxidative stress in the human eye. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between CYP2E1 (rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management.A total of 600 NPC cases and 545 controls frequency‐matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of CYP2A6 and CYP2E1(rs3813867) was performed by polymerase chain reaction restriction (PCR)‐fragment length polymorphism (RFLP) analysis and the GSTM1 (rs1183423000) and GSTT1(rs1601993659) genetic variations were evaluated using the PCR technique.The genotype distributions of CYP2E1(rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) genotypes did not differ significantly among NPC cases and controls (p > 0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking.In this large studied North African population, our findings suggest that the functional CYP2E1, CYP2A6, GSTM1 and GSTT1 variations did not influence NPC susceptibility. [ABSTRACT FROM AUTHOR]

Abstract 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.

Oxidative stress is involved in the development of systemic lupus erythematosus (SLE). It is well known that activity of the glutathione S-transferase superfamily has a protective effect against oxidative stress. Several studies have investigated the association between the GSTT1/GSTM1 polymorphisms and the risk of SLE with inconsistent results. The present meta-analysis was performed to investigate the association between susceptibility to SLE and the null genotypes of GSTT1 and GSTM1. Eligible publications were identified by searching several databases, 18 case-control studies with 2483 cases and 3643 controls met the inclusion criteria. The raw data of three reports have internal inconsistencies, therefore these studies were excluded from the final analysis. The results showed that the GSTM1 null genotype significantly increased the risk of SLE (OR = 1.17, 95 % CI: 1.03-1.32, p = 0.012) with no evidence of significant heterogeneity (Q = 14.53, df = 14, p = 0.411; I² = 3.4 %). The GSTT1 null genotype was not associated with the risk of SLE (OR = 0.94, 95 % CI: 0.80-1.10, p = 0.447). There was no evidence of heterogeneity between studies. The present study showed that the null genotype of GSTM1 was weakly associated with the risk of SLE.

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. What is the central question of this study?Genetic variations in the GSTT1 and GSTM1 enzymes that detoxify cigarette smoke products might be correlated to chronic obstructive pulmonary disease (COPD) development: do GSTT1 and GSTM1 polymorphisms modulate the risk for COPD in North Indians and what is the relationship with associated clinical parameters?What is the main finding and its importance?The GSTT1(−) null genotype was strongly correlated with COPD development, and GSTT1 deletion was also linked with higher Global Strategy for Obstructive Lung Disease (GOLD) grading. At the same time, no association was observed in the GSTM1(−) null genotype in the North Indian COPD patients. [ABSTRACT FROM AUTHOR]

Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: In the present case-controlled study, we explored the role of genetic polymorphism in three xenobiotic metabolizing genes, GSTM1, GSTT1 and GSTP1, and their association to gallbladder cancer (GBC) risk in a North Indian population. Its etiology is influenced by genetic, food habits, lifestyle, and environmental factors. GBC incidence is significantly higher in the Gangetic belt, India. Therefore, we explored the prognostic factors in the susceptibility of GBC through gene–gene and gene–environment interaction in this region. Material and Methods: Genetic polymorphism was analyzed in 108 GBC patients from Kamala Nehru Memorial Cancer Hospital, Prayagraj and 142 matched controls. GSTM1 and GSTT1 genotypes were analyzed by multiplex PCR method, while restriction fragment length polymorphism (RFLP) was performed to analyze GSTP1 genotypes. Logistic regression analysis calculating the odds ratio (OR) and 95% confidence interval (CI) was performed to analyze the GBC risk. Results: GSTT1 (null) genotype was at a significantly higher risk and susceptible to GBC (OR = 2.044, CI = 1.225–3.411, P = 0.006), while GSTM1 and GSTP1 genotypes did not show any association to GBC risk. After sex stratification, females diagnosed with GBC had higher GSTT1 (null) genotype (OR = 2.754, CI = 1.428–5.310, P = 0.003) compared to males. GBC patients dwelling in rural areas show higher GSTT1 (null) genotype with two-fold GBC risk (OR = 2.031, CI = 1.200–3.439, P = 0.008). Further, GBC patients with histopathology of adenocarcinoma also showed higher GSTT1 (null) genotype (OR = 2.113, CI = 1.248–3.578, P = 0.005). Gene–gene interaction between GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val), enhance the GBC risk (OR = 1.840, CI = 1.135–2.982, P = 0.013). Conclusions: The present study suggests that GSTT1 (null) genotype has higher susceptibility and risk towards GBC in North Indian population. Female patients, patients with histopathology of adenocarcinoma and rural dwelling GBC patients have higher GSTT1 (null) genotypes and may be at risk of developing GBC. The genotype combination GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val) has increased GBC susceptibility and may be considered as 'at risk' genotypes for GBC in North Indians. [ABSTRACT FROM AUTHOR]

Glutathione S‐transferase theta 1 (GSTT1) is an enzyme involved in phase II biotransformation processes and a member of a multigene family of detoxifying and clearing reactive oxygen species. GSTT1 is polymorphic like other biotransforming enzymes, allowing variability in hepatic conjugation processes. Immunological recognition of the GSTT1 alloantigen, as evidenced by donor‐specific antibodies formation, has previously been observed in recipients lacking GSTT1 protein (called GSTT1−, GSTT*0, null phenotype or homozygous for the GSTT1 deletion) who receive liver or kidney transplants from GSTT1+ donors and is a risk factor for the development of de novo hepatitis following liver transplants from a GSTT1 expressing donor. Antibodies against GSTT1 are demonstrated in patients who are GSTT1 null and received a transplant from a GSTT1+ donor. Understanding the local population frequency of the GSTT1 deletion is of value in understanding the potential clinical risk of developing post‐transplant complications, which can be attributed to the nonexpression of GSTT1. A population of 173 healthy donors of the Murcia Region in Southeast Spain was evaluated for a null allele of GSTT1 (n = 173). DNA was extracted, and GSTT‐1 null allele detection was performed by real‐time polymerase chain reaction. The frequency of the null GSTT1 genotype (nonexpression or deletion of the homozygous polymorphism of the GSTT1 protein) was 17.9% (n = 31 null allele GSTT1/173 total individuals). Our data suggest that the frequency of null GSTT1 mutations in our population in Southeast Spain is 17.9%, lower than in other Caucasoid populations. This would convert our recipient population into more susceptible to nonlocal potential organ donors and less susceptible to local donors. All recipients bearing this GSTT1 deletion homozygous would be without the protein and triggering an alloantigen in the case of transplantation with a donor without deletion. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common malignant tumor of the endocrine system, and its incidence is increasing worldwide each year. This study aimed to explore the association between XRCC1, GSTM1, and GSTT1 polymorphisms in the model of thyroid cancer. The experiment was conducted by searching PubMed, Embase, and Web of Science, with the last search performed in March 2022. A total of 12 studies were included in this meta-analysis, with sample sizes ranging from 211 to 1124. The proportion of XRCC1 polymorphisms (rs25489, GG) in thyroid cancer was slightly lower than that of the normal control group, but the difference was not statistically significant (Mean difference=1.13, 95% CI: 0.99–1.28, p=0.08). The proportion of XRCC1 polymorphisms (rs25489, GA) in thyroid cancer was significantly lower than that of the normal control group (Mean difference=1.32, 95% CI: 1.16–1.52, p<0.00001). The proportion of XRCC1 polymorphisms (rs25489, AA) in thyroid cancer was slightly lower than that of the normal control group, but again, the difference was not statistically significant (Mean difference=0.78, 95% CI: 0.61–1.01, p=0.06). Similarly, the proportion of XRCC1 polymorphisms (rs25487, GG) and (rs25487, GA) in thyroid cancer was lower than that of the normal control group, but the differences were not statistically significant (p=0.22 and p=0.49, respectively). In conclusion, this study found that the proportion of XRCC1 polymorphisms (rs25489, AA) in thyroid cancer was lower than that of the normal control group. [ABSTRACT FROM AUTHOR]

Chloroform accumulation in the body and the increase in its steady-state concentrations in blood of exposed people have been established to be associated with polymorphisms of enzyme genes in a genotype involved in metabolism of water disinfection byproducts (A415G of EPHX1 gene, C1091T of CYP2E1 gene, zero mutations of GSTT1 and GSTM1 genes) (р < 0.000001). These polymorphisms in a genotype correlate with higher chloroform levels in blood of people consuming chlorinated drinking water: by 43.8 % and higher for GSTM1 gene polymorphism; by 68.2 % and higher for GSTT1; by 80.4 % and higher for EPHX1 (р < 0.01). EPHX1 genetic polymorphism makes chloroform accumulation much more probable (levels in blood ≥ Р75), which is the most pronounced when combined with GSTТ1 genetic polymorphism. The study results allow us to consider hetero- and homozygous polymorphic genotypes AG/GG for the EPHX1 gene, CT/TT for the CYP2E1 gene, and the null allele in the GSTT1 and GSTM1 genes as genetic predisposition factors for chloroform accumulation in the body. This increases the probability of health outcomes associated with chronic exposure to this disinfection byproduct. The A415G polymorphism of the EPHX1 gene and null alleles of GSTT1 gene, their combinations including the combination with the null allele of the GSTM1 gene and/or the C1091T polymorphism of the CYP2E1 gene can be used as the most informative biomarkers of sensitivity when assessing risks associated with exposure to trihalomethanes (chloroform) at levels not exceeding MPC in water.

Purpose: Chemotherapy induced peripheral neuropathy (CIPN) is a debilitating condition that is a direct consequence of receiving cancer treatment. The molecular aetiology of CIPN is not well understood, and it is theorised that there may be a genetic component. Genetic polymorphisms in Glutathione-S Transferase (GST) genes, including GSTT1, GSTM1 and GSTP1, encode for enzymes known to metabolise drugs used in chemotherapy, and have been theorised to be associated with CIPN. This study aimed to investigate four markers in these genes for an association in a mixed cancer cohort in relation to CIPN (n = 172). Methods: CIPN was measured using the neuropathy item from the Patient Reported Outcome Common Terminology Criteria for Adverse Event (PRO-CTCAE) assessment. Genotyping for all samples was performed using PCR for the GSTM1 and GSTT1 null variants and restriction fragment length polymorphisms for the GSTP1 and GSTM1 polymorphisms. Results: No associations were found for the GST gene markers in relation to CIPN within our study, or CIPN severity. Longitudinal stratification of the CIPN phenotypes to examine links for neuropathy, identified nominally significant protective associations with the GSTM* null allele (p-value = 0.038, OR = 0.55) and the presence of pain at month 2 of treatment, as well as a risk factor for pain related month 2 of treatment for individuals with the GSTT1*null allele (p-value = 0.030, OR = 1.64). Higher severity of pain in patients with CIPN persisted at each time-point compared to those without CIPN. Conclusion: No significant results for an association between CIPN with polymorphisms in GSTM1, GSTT1 and GSTP1 were identified. However, associations for the GSTM1¬-null and GSTT1-null polymorphisms with pain at month 2 following chemotherapy were identified. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the role of glutathione-S-transferase gene (GSTM1 and GSTT1) polymorphisms in the predisposition of type 2 diabetes mellitus (T2DM) with or without diabetic retinopathy (DR). Methods: The case-control study included 188 subjects: 50 T2DM with DR, 63 T2DM without DR, and 75 healthy individuals' presenting no clinical signs or evidence of diabetes mellitus. Zinc and magnesium levels were measured using a flame atomic absorption spectrophotometer, and the lipid profile was evaluated using standard methods. The gene polymorphism of GSTs was performed by the multiplex-PCR method. Results: Compared to the control, DR and T2DM had considerably greater total cholesterol, LDL-C, and decreased HDL-C levels. Magnesium levels were significantly lower in DR and T2DM than in control. Total cholesterol, LDL, TG, and magnesium levels didn't differ significantly between DR and T2DM groups. In DR, the GSTT1-null genotype was more prevalent than in T2DM subjects and controls (26.0%, 12.7%, and 10.7%, respectively). GSTT1-null genotype was considerably more common in DR than in controls and associated with 2.94-folds enhancing the chance of developing DR (OR = 2.94; 95% CI = 1.12–7.75; p = 0.02). However, the recurrence of GSTM1-null genotype was not clearly distinguishable among these three populations (28.0%, 38.1% and 29.3%, respectively) and not particularly prone to the risk of DR compared to T2DM subjects and controls (OR = 0.63; 95% CI = 0.28–1.41; p = 0.26; OR = 0.94; 95% CI = 0.42–2.07; p = 0.87, respectively). Conclusions: Taken together, these findings suggest the potential role of GSTT1 deletion mutation as a risk factor for the vulnerability of DR among T2DM patients in the Bangladeshi population. [ABSTRACT FROM AUTHOR]

Heavy metal ions are known to induce generation of a large number of reactive oxygen species (ROS). Glutathione S-transferases (GSTs) play an important role in adaptation and response to oxidative stress. GSTM1, GSTT1, and GSTP1 genes have numerous described polymorphisms, the most significant being GSTM1, GSTT1, and GSTP1 Ile105Val deletion ones. Our objective was to study the relationship between the genetic polymorphism of GSTM1, GSTT1, GSTP1 genes and blood levels of metals in smelter operators engaged in crude lead refining. We examined 55 male lead-refining furnace operators working at a non-ferrous metal alloy plant. Blood metal concentrations were measured by inductively coupled plasma mass spectrometry. GSTM1 and GSTT1 deletion polymorphisms were determined using real-time SYBR Green qPCR and that of GSTP1 Ile105Val – using a commercial SNP Screening Kit. Statistical data processing was carried out using the Mann – Whitney U-test. Blood levels of industry-specific metals were not statistically different between the workers with GSTT1 and GSTP1 genotypes. We established, however, that men with the null genotype of GSTM1 had significantly higher blood arsenic levels. Our findings indicate that a high blood arsenic level associated with occupational exposure may be attributed to the GSTM1 null genotype. This observation can be used to identify the most vulnerable groups of individuals at risk of overexposure to arsenic.

Objectives: Obesity is a complex multifactorial disease with recently increasing prevalence and incidence. Several studies have been conducted to explain the ethiology, pathophysiology, epidemiology, molecular and genetic mechanisms, and effective treatments of obesity. Glutathione S-transferase (GST) S1, GSTZ1, and GSTT1 are essential enzymes for oxidative stress and metabolism-related disorders. For this purpose, we aimed to reveal the role of GSTS1, GSTZ1, and GSTT1 in obesity. Methods: The gastric tissue samples were taken from the patients diagnosed with obesity who underwent bariatric surgery in Ankara Keçiören Training and Research Hospital General Surgery Clinic between 2017 and 2019. Immunostaining was performed on paraffin-embedded tissues to evaluate GSTS1, GSTZ1, and GSTT1 expressions. Laboratory data of the patients were recorded. All the results were analyzed statistically. Results: Weak GSTS1 expression was observed in 38.1% of tissues and moderate in 6.3%. 37.3% of the tissues presented weak GSTZ1 expression, and 11 (8.7%) displayed moderate. There were weak GSTT1 expressions in 7.1% of the tissues and moderate 0.8% of them. A positive and statistically significant correlation was observed between GSTS1 and GSTT1 expression levels ((r) = 0.028, p = 0.010; p < 0.05). There were no significant differences between expression levels and gender, age, comorbidities, and medication usage (p > 0.05). Conclusions: GSTs, in particular GSTS1, GSTT1, and GSTZ1, might contribute to molecular mechanisms and the progression of obesity. In our study, GSTS1, GSTT1, and GSTZ1 were found to be moderately expressed in gastric tissues taken from obese patients. However, new studies using more samples and advanced techniques are needed to elucidate the relationship. [ABSTRACT FROM AUTHOR]

Backgrounds: Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit affecting most teenagers and numerous adults throughout the world. The present study was designed to assess the association of the presence or absence of GSTM1, GSTT1, and single nucleotide polymorphisms rs1695 in GSTP1 and rs1042522 in TP53 gene with acne vulgaris. Methods: The cross‐sectional case–control study was conducted at the Institute of Zoology from May 2020 to March 2021 and included acne vulgaris patients (N = 100) and controls (N = 100) enrolled in Dera Ghazi Khan district, Pakistan. Multiplex and tetra‐primer amplification refractory mutation system‐polymerase chain reactions were applied to investigate the genotype in analyzed genes. The association of rs1695 and rs1042522 with acne vulgaris was studied either individually or in various combinations with GATM1 and T1. Results: A significant association of absence of GSTT1 and mutant genotype at rs1695 (GG) and at rs1042522 (CC) in GSTP1 and TP53, respectively, was found to be associated with acne vulgaris in enrolled subjects. Subjects aged 10–25 years and smokers were more susceptible to acne vulgaris. Conclusion: Our results suggest that genotypes of glutathione S‐transferases (GSTs) and TP53 are involved in protection against oxidative stress and may influence disease progression in acne vulgaris. [ABSTRACT FROM AUTHOR]

Oxidative stress has a fundamental role in the pathophysiology of various conditions, like infertility. This case-control study was performed to assess the potential role of CYP19A1, GSTM1, and GSTT1 in modifying individual predisposition to female infertility. Genotyping of 201 women with established infertility and 161 fertile female controls was performed, and statistical associations were analyzed. For carriers of GSTM1 null genotype along with CYP19A1 C allele, there is a significant association with female infertility risk (OR 7.023; 95% CI (3.627–13.601; p < 0.001), and, also for carriers of GSTT1 null genotype along with the CYP19A1 TC/CC genotype (OR 24.150; 95% CI (11.148–52.317; p < 0.001). A positive association with female infertility risk for carriers of the C allele in CYP19A1 and null genotypes in GTSM1 (OR 11.979; 95% CI (4.570–31.400; p < 0.001) or GSTT1 (OR 13.169; 95% CI (4.518–38.380; p < 0.001) was found. When both GSTs are deleted, the risk of developing female infertility is significant, independently of the CYP19A1 genotype; when all the presumed high-risk genotypes are present, we found a significant association with female infertility risk (OR 47,914; 95% CI (14,051–163,393; p < 0.001). [ABSTRACT FROM AUTHOR]

Abstract Background Glutathione S-transferases (GSTs) are a class of important Phase II detoxification enzymes that catalyze the conjugation of glutathione and xenobiotic compounds (environmental carcinogens, pollutants and drugs) to protect against oxidative stress. GSTT1 and GSTM1 genetic polymorphisms have been extensively studied, and null genotypes or homozygous deletions have been reported in various populations. Previous studies have suggested that those who are homozygous null at the GSTM1 or GSTT1 loci are more susceptible and have a higher risk of cancers linked to environmental pollutants and drug-induced toxicity. Our study focused on GSTM1 and GSTT1 null allele frequency in the Doon population of Himachal Pradesh (India) with a comparison across other Inter and Intra-Indian ethnic groups to predict variation in the possible susceptible status. Material and methods Genomic DNA samples were extracted from 297 healthy unrelated individuals by a ReliaPrep™ Blood gDNA Miniprep kit (Promega, USA), and genotyped for allelic variation in GSTM1 and GSTT1 genotypes by multiplex polymerase chain reaction. Fisher's exact test was applied using SPSS.20 to analyze the genotypic distribution of GSTM1 and GSTT1 null alleles in male and female of Doon region (Solan) Himachal Pradesh. Results In our study, the frequency distribution of the homozygous null genotypes of GSTM1, GSTT1 individually as well as combined was found as 33.3%, 32% and 9%, respectively. Upon gender-wise comparison, a non-significant distribution (p > 0.05) for null genotypes of GSTM1 (32.8% and 35.4%, OR-0.77, 95% CI 0.42–1.41), GSTT1 (33.2% and 27.7%, OR-1.12, 95% CI 0.63–2.0) individually and combined GSTM1 and GSTT1 (10.8% and 3.7%, OR-0.31, 95% CI 0.07–1.42) were observed in studied population. Conclusions In our studied population, the frequency of GSTM1 null genotypes was found deviated from Inter- and Intra-Indian ethnic groups. However, the frequency of homozygous null type of GSTT1 was not significantly different, when compared to previous Indian studies, comparison with global ethnic groups showed deviation. Thus, our study has highlighted possible susceptibility risk to various xenobiotics in the Doon population of Himachal Pradesh, India.

Ezeldine K Abdalhabib,1 Badr Alzahrani,1 Fehaid Alanazi,1 Abdulrahman Algarni,2 Ibrahim Khider Ibrahim,3 Hozifa A Mohamed,4,5 Hassan A Hamali,6 Abdullah A Mobarki,6 Gasim Dobie,6 Muhammad Saboor6,7 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia; 2Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Borders University, Arar, Saudi Arabia; 3Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 4Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 5Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Sudan International University, Khartoum, Sudan; 6Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 7Medical Research Center (MRC), Jazan University, Jazan, Saudi ArabiaCorrespondence: Muhammad Saboor, Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan, Saudi Arabia, Tel +966 54 495 9029, Email msaboor@jazanu.edu.saPurpose: Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL.Patients and Methods: This case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control.Results: The genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = < 0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42– 29.74, P < 0.001).Conclusion: Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.Keywords: GSTT1, GSTM1, polymorphism, acute lymphoblastic leukemia

Objective: Chronic periodontal disease (CP) is a multifactorial infectious and inflammatory disease that occurs due to the challenge between the immune response of the host and specific periodontal bacteria, and that can lead to tooth loss due to damage inflicted to the supporting tissue. The current study investigates the genotypes of the GSTM1 and GSTT1 genes, along with the allelic frequency of the single nucleotide polymorphism [SNP; rs1695] in the GSTP1 gene and correlates them individually or in various combinations with the incidence of CP. Methods: A total of 203 clinically confirmed CP patients and 201 control subjects were enrolled from Multan and Dera Ghazi Khan Districts in Pakistan from April to July 2022. Multiplex Polymerase Chain Reaction (PCR) and tetra-primer amplification refractory mutation system–polymerase chain reaction (T-ARMS–PCR) approaches were applied to determine the genotypes of the studied GSTs. The association of rs1695 in GSTP1 with CP was studied both individually and in various combinations with GSTM1 and T1. Results: The absence of GSTM1, the presence of GSTT1 and the presence of the mutant allele (G) at rs1695 in GSTP1 were found to be significantly associated with CP. Patients aged between 10 and 30 years were more affected by CP. Conclusion: Our results indicate that the genotypes of the analyzed GSTs affect the levels of protection from oxidative stress and may therefore influence the disease progression in CP. [ABSTRACT FROM AUTHOR]

Introduction: Coronary artery disease (CAD) is the most common type of heart disease and so it is important to identify risk factors of CAD. Reactive oxygen species (ROS) contribute to the genesis and the progression of CAD by affecting different pathways. The glutathione S-transferase is an enzyme that reduces ROS in the body. Therefore, polymorphisms that affect the activity of these enzymes must be recognized. Methods: After collecting samples from 191 CAD patients and 191 healthy individuals identified by a cardiologist, the multiplex-polymerase chain reaction (multiplex-PCR) technique was used to diagnose null genotypes of glutathione S transferase T1(GSTT1) and M1(GSTM1). The lipid profile was assessed by the conventional colorimetric method. Results: The results indicated that the frequency of null genotypes of GSTM1 and GSTT1 in patients was 49.7% and 21.5%, respectively. However, in the control group, it was 37.7% and 16.8%, respectively. Only the null genotype of GSTM1 was associated with CAD (P=0.018, OR=1.46). Further analysis confirmed that the GSTM1 null genotype was not a significant risk factor for early-onset CAD (P=0.169). Conclusion: In conclusion, the GSTM1 null genotype is involved in the susceptivity to CAD in the study population. [ABSTRACT FROM AUTHOR]

Background: In this study we explored the association of polymorphisms of glutathione s transferase gene including GSTM1, GSTT1 and GSTP1 with adverse acute normal tissue reactions resulted from radiotherapy in HNC patients. We assessed the association of GSTM1 and GSTT1 null genotypes and Ile105Val of exon-5 and Ala114Val of exon-6 of GSTP1 gene polymorphisms with the risk of acute skin toxicity reactions after therapeutic radiotherapy in HNC patients., Methods: Four hundred HNC patients administered with Intensity modulated radiation therapy were enrolled in this study for the evaluation of radiotherapy associated toxicity reactions. The genotyping of GSTM1 and GSTT1 were performed by polymerase chain reaction (PCR). The GSTP1 Ile/Val of exon-5 and Ala/Val of exon-6 polymorphism was determined by PCR followed by restriction fragment length polymorphism (PCR-RFLP)., Results: The univariate logistic regression analysis showed that GSTM1 and GSTT1 null genotypes were not associated with either skin reaction or oral mucositis in response to radiotherapy induced after effects. When we studied, A313G polymorphism at exon 5 and C341T polymorphism at exon 6 of GSTP1 gene, majority of genotypes were wild type A/A genotype for exon 5 showed non-significant association with Skin reactions whereas, C/T genotype of exon-6 showed significant negative association with skin reactions., Conclusion: The findings obtained from this study concluded that the null genotypes of GSTM1 and GSTT1 gene polymorphisms showed no association with radiotherapy induced acute toxicities such as dermatitis and oral mucositis. The results indicated negative association of heterozygous C/T genotype of exon-6 of GSTP1 with acute skin reactions.

Mutations in genes encoding proteins necessary for detoxifying oxidative stress products have been predicted to increase susceptibility to lung cancer (LC). Despite this, the association between waterpipe tobacco smoking (WP), genetic polymorphisms, and LC risk remains poorly understood. This is the first study to explore the relationship between WP tobacco smoking and these genetic factors. Previously, we investigated the association of GSTP1 SNPs (rs1695-A/G and rs1138272-C/T) with LC in Iraqi males who smoke WP. Here, we expanded our analysis to include GSTM1 (active/null) and GSTT1 (active/null) genotypes, both individually and in combination with GSTP1 SNPs. Multiplex PCR and RFLP-PCR assays were utilized to determine the genotypes of 123 cases and 129 controls. No significant association was observed between GSTM1-null or GSTT1-null genotypes and LC risk, either separately or in combination with variant genotypes of GSTP1 (rs1695 "AG+GG" and rs1138272 "CT+TT"). However, smoking WP and carrying null genotypes elevated the risk five-fold for GSTM1-null (OR 5.17, 95 % CI 2.02-13.24, P<0.001) and three-fold for GSTT1-null (OR 3.08, 95 % CI 1.55-6.13, P=0.001) compared to non-smokers carrying active genotypes. Conversely, genotype distribution analysis based on LC histological types did not indicate an increased risk of LC. Lung cancer is a complex multifactorial disease. WP smoking and GSTs genetic polymorphisms might be associated with an increased risk of developing LC. However, our data did not confirm an association between GST polymorphisms alone and the risk of LC., Competing Interests: Declaration of Competing Interest None of the authors have any non-financial conflict of interest. The authors also declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Studies have shown that glutathione S-transferase M1 (GSTM1) and. glutathione S-transferase T1 (GSTT1) null genotype may increase the risk of cervical cancer (CC) or ovarian cancer (OC), however, the results of published original studies and meta-analyses are inconsistent.Objectives: To investigate the association between GSTM1 present/null and GSTT1 present/null polymorphisms, with the risk of cervical cancer or ovarian cancer.Methods: The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between GSTM1 present/null and GSTT1 present/null polymorphisms and the risk of cervical cancer or ovarian cancer. To assess the confidence of statistically significant associations, we applied false positive reporting probability (FPRP) and bayesian false discovery probability (BFDP) tests.Results: Overall analysis showed that GSTM1 null was associated with an increased risk of cervical cancer, and subgroup analysis showed a significant increase in cervical cancer risk in Indian and Chinese populations; GSTT1 was not found null genotype are significantly associated with cervical cancer. Overall analysis showed that GSTM1 and GSTT1 null were not associated with the risk of ovarian cancer, subgroup analysis showed that GSTM1 null was associated with an increased risk of OC in East Asia, and GSTT1 null was associated with an increased risk of OC in South America. However, when we used false positive reporting probability and bayesian false discovery probability to verify the confidence of a significant association, all positive results showed “low confidence” (FPRP > .2, BFDP > .8).Conclusion: Overall, this study strongly suggests that all positive results should be interpreted with caution and are likely a result of missing plausibility rather than a true association.

Backgrounds: Compared with previously published meta-analyses, this is the first study to investigate the combined effects of glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1 IIe105Val) and type 2 diabetes mellitus (T2DM) risk; moreover, the credibility of statistically significant associations was assessed; furthermore, many new original studies were published. Objectives: To determine the relationship between GSTM1, GSTT1, and GSTP1 polymorphisms with T2DM risk. Methods: PubMed, Embase, Wanfang, and China National Knowledge Infrastructure Databases were searched. We quantify the relationship using crude odds ratios and their 95% confidence intervals Moreover, the Venice criteria, false-positive report probability (FPRP), and Bayesian false discovery probability (BFDP) were used to validate the significance of the results. Results: Overall, significantly increased T2DM risk was found between individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on T2DM risk, but, combined effects of the GSTT1 and GSTP1 polymorphisms was not statistically significant. GSTT1 gene polymorphism significantly increases the risk of T2DM complications, while GSTM1 and GSTP1 polymorphisms had no statistical significance. The GSTM1 null genotype was linked to a particularly increased risk of T2DM in Caucasians; the GSTT1 null genotype was connected to a significantly higher risk of T2DM in Asians and Indians; and the GSTP1 IIe105Val polymorphism was related to a substantially increased T2DM risk in Indians. Moreover, the GSTM1 and GSTT1 double null genotype was associated with substantially increased T2DM risk in Caucasians and Indians; the combined effects of GSTM1 and GSTP1 polymorphisms was associated with higher T2DM risk in Caucasians. However, all significant results were false when the Venice criteria, FPRP, and BFDP test were used (any FPRP >0.2 and BFDP value >0.8). Conclusion: The current analysis strongly suggests that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms might not be connected with elevated T2DM risk. [ABSTRACT FROM AUTHOR]

In Peru, 24,581 people were diagnosed with tuberculosis (TB) in 2020. Although TB treatments are effective, 3.4–13% are associated with significant adverse drug reactions (ADRs), with drug-induced liver injury (DILI) considered the most predominant. Among the first-line antituberculosis drugs, isoniazid (INH) is the main drug responsible for the appearance of DILI. In the liver, INH is metabolized by the enzymes N-acetyltransferase-2 (NAT2), cytochrome P450 2E1 (CYP2E1), and glutathione S-transferase (GST) with two isoforms, GSTT1 and GSTM1. Based on previous studies, we hypothesized that interactions between the GSTT1 and GSTM1 null genotypes induce DILI in TB patients. In this cross-sectional study of 377 participants who completed their anti-TB treatment, we genotyped by revealing the presence or absence of 215- and 480-bp bands of GSTM1 and GSTT1, respectively. We found that the prevalence of the GSTM1 genotype was 52.79% and 47.21% for presence and null, respectively, and for GSTT1 it was 69.76% and 30.24% for presence and null, respectively. Neither genotype was prevalent in the patients who developed DILI (n = 16). We did not confirm our hypothesis; however, we found that the combination of GSTM1 present genotype, GSTT1 null genotype, fast NAT2 acetylators, and CYP2E1 c1/c1 genotype had a significant risk for the development of ADR (OR 11; p = 0.017; 95% CI: (0.54–186.35)). We propose that the presence of the GSTM1 present genotype, GSTT1 null genotype, fast NAT2 acetylators, and CYP2E1 c1/c1 genotype in the Peruvian population could be considered a risk factor for the development of ADR due to therapeutic drug intake. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Essential hypertension (EH) results from a complex interaction between environmental factors and an individual’s genetic background. Aim To assess the relationship between polymorphisms in GSTM1 and GSTT1 and the risk of EH. Subjects and methods A multiplex-PCR was used to identify the genotypic profiles of GSTM1 and GSTT1 in 160 patients and 210 controls. Results The frequency of GSTM1-null genotype was higher in patients younger than 61 years when compared to those over 61 years. Interestingly, GSTT1-null was significantly associated with the risk of EH (OR 4; 95% CI 2.6–6.3; p

The pathogenesis of Cystic Fibrosis (CF) airway disease is not well understood. CF is an autosomal recessive monogenic genetic disease. It affects the exocrine glands, which normally produce thin secretions such as mucus, sweat and tears. In CF, the mucus is thick and sticky which interferes with certain normal organs. A broad knowledge of the genes which are involved in the regulation or co-regulation of affected organs in the CF is required to get a better understanding of its pathophysiological mechanisms. DNA microarray approaches have made it possible to get an insight on gene expression across the genome. In the current study, microarray data related to CF and CF-associated affected organs were retrieved from the NCBS Gene Expression Omnibus database and were subjected to gene regulatory network analysis. We constructed two separated networks of up and down regulated genes from six microarray datasets. The power-law obeying topological properties showed scale-free hierarchical nature of the both networks. Density and compactness of both networks at each level was calculated by modularity and Hamiltonian energy. From all the leading hubs we found four key genes namely GSTT1, ANKRD7, PBX1, and TGFB2 deeply rooted in up and down regulated networks respectively. Conclusively these genes may have prognostic significance.

Abstract Serous ovarian cancer (SOC) is the most common women cancer and the leading cause of cancer-related mortality among the gynaecological malignancies. Although effective chemotherapeutics combined with surgery are developed for the treatment, the five-year survival rate is unsatisfactory due to chemoresistance. To overcome this shortcoming of chemotherapy, we established taxol and carboplatin resistant SOC cell lines for the understandings of the molecular and cellular mechanisms of chemoresistance. Here, we found that these chemoresistant cell lines showed less viability and proliferation, due to more cells arrested at G0/G1 phase. Glutathione-S-transferases-theta1 (GSTT1) was significantly upregulated in these chemoresistant cells, along with other chemoresistant genes. Meanwhile, GSTT1 expression was also significantly upregulated in the SOC patient tissues after taxol treatment, indicating this upregulation was physiologically relevant to chemotherapy. Further, suppression of GSTT1 expression by shRNA in SOC cell lines led to more sensitivity to drug treatment, through increasing divided cells and promoting cell death. Moreover, the expression of DNA topoisomerase 1 (Topo I) was in synergy with that of GSTT1 in the chemoresistant cells, and GSTT1 can bind to Topo I in vitro, which suggested GSTT1 could function through DNA repair mechanism during chemoresistance. In summary, our data imply that GSTT1 may be a potential biomarker or indicator of drug resistance in serous ovarian cancer.

Background: Several meta-analyses have analyzed the association of GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val polymorphisms with leukemia risk. However, the results of these meta-analyses have been conflicting. Moreover, they did not evaluate the combined effects of the three aforementioned gene polymorphisms. Furthermore, they did not appraise the credibility of the positive results. Finally, many new studies have been published. Therefore, an updated meta-analysis was conducted.Objectives: To further explore the relationship of the three aforementioned gene polymorphisms with leukemia risk.Methods: The crude odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the association of the individual and combined effects of the three aforementioned genes. Moreover, the false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP) were applied to verify the credibility of these statistically significant associations.Results: Overall, the individual GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms added leukemia risk. On combining GSTM1 and GSTT1, GSTM1 and GSTP1, and GSTT1 and GSTP1 polymorphisms, positive results were also observed. However, no significant association was observed between the combined effects of these three polymorphisms with leukemia risk in the overall analysis. Moreover, when only selecting Hardy–Weinberg equilibrium (HWE) and medium- and high-quality studies, we came to similar results. However, when the FPRP and BFDP values were applied to evaluate the credibility of positive results, the significant association was only observed for the GSTT1 null genotype with leukemia risk in Asians (BFDP = 0.367, FPRP = 0.009).Conclusion: This study strongly suggests a significant increase in the risk of leukemia in Asians for the GSTT1 null genotype.

Abstract Objective Glutathione S-transferases have been associated with experimental resistance to some drugs. The present study investigated the factors associated with blood pressure control in patients with essential hypertension, especially the role of GSTT1 and GSTM1 genes polymorphisms. This cross-sectional study in Burkina Faso consisted of 200 patients with essential hypertension and under treatment. Results In the present study, 57.5% (115/200) of patients had their hypertension under control. No statistically significant difference was found between controlled and uncontrolled groups for anthropometric and biochemical parameters as well as for GSTT1 or GSTM1 gene polymorphisms (all p > 0.05). Current alcohol consumption (OR = 3.04; CI 1.88–6.13; p

Background: Fourteen meta-analyses reported the individual effects of the GSTM1 and GSTT1 polymorphisms on leukemia risk. However, over 40 studies were not included in previously published meta-analyses. Moreover, one key aspect was that previous metaanalyses did not conduct the false-positive test on the aforementioned issues. Furthermore, previous meta-analyses did not observe the combined effects of GSTM1 present/null and GSTT1 present/null polymorphism with leukemia risk. Therefore, we conducted the current study to further analyze these associations. Objectives: This study aimed to investigate the association between the individual and combined effects of the GSTM1 present/null and GSTT1 present/null polymorphisms and the risk of leukemia. Methods: A meta-analysis was performed applying Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Moreover, false-positive report probability (FPRP) and Bayesian false discovery probability (BFDP) were applied to investigate the false-positive results. Results: The individual GSTM1 and GSTT1 null genotypes and combined effects of the two genes were associated with a significantly increased leukemia risk in overall and several subgroup analyses, such as Asians, Caucasians, and so on. Then, further analysis was conducted using FPRP and BFDP. Significant associations were considered as "positive" results on the GSTM1 null genotypewith leukemia risk in overall populations (FPRP < 0.001 and BFDP = 0.006), Asians (FPRP < 0.001 and BFDP < 0.001), and East Asian population (FPRP < 0.001 and BFDP = 0.002). For the GSTT1 null genotype, significant associations were regarded "positive" results in overall populations, acute myeloid leukemia (AML), Asians, and East Asian population. For the combined effects of the GSTM1 and GSTT1 polymorphisms, significant associations were also considered "positive" results in the overall analysis of Asians, Indians, and East Asian population. Conclusion: This study strongly indicates that the individual GSTM1 and GSTT1 null genotypes and combined effects of the two genes are associated with increased leukemia risk in Asians, especially in the East Asian population; the GSTT1 null genotype is associated with increased AML risk; the combined effects of the two genes are associated with increased leukemia risk in Indians. [ABSTRACT FROM AUTHOR]

Context: Lung cancer pathological process involves cumulative effects exerted by gene polymorphism(s), epigenetic modifications, and alterations in DNA repair machinery. Further, DNA damage due to oxidative stress, chronic inflammation, and the interplay between genetic and environmental factors is also an etiologic milieu of this malignant disease.Aims: The present study aims to assess the prognostic value of DNA repair, cytokines, and GST gene polymorphism in lung cancer patients who had not received any neoadjuvant therapy.Materials and Methods: In this case-control study, 127 cases and 120 controls were enrolled. DNA from the blood samples of both patients and controls was used to genotype XRCC1Arg399Gln, XPDLys751Gln, and interleukin-1 (IL-1β) genes by polymerase chain reaction (PCR)-restriction fragment length polymorphism method, whereas multiplex PCR was performed to genotype GSTT1 and GSTM1.Results: Binary logistic regression analysis showed that XRCC1Arg399Gln-mutant genotype (Gln/Gln, odds ratio [OR] = 4.6, 95% confidence interval [CI]: 2.2-9.6) and GSTT1 null (OR = 2.7, 95% CI: 1.6-4.5) were linked to cancer susceptibility. Generalized multidimensional reduction analysis of higher order gene-gene interaction using cross-validation testing (CVT) accuracy showed that GSTT1 (CVT 0.62, P = 0.001), XPD751 and IL-1β (CVT 0.6, P = 0.001), and XRCC1399, XPD751, and interleukin-1 receptor antagonists (IL-1RN) (CVT 0.98, P = 0.001) were single-, two-, and three-factor best model predicted, respectively, for lung cancer risk. Classification and regression tree analysis results showed that terminal nodes which contain XRCC1399-mutant genotype (AA) had increased the risk to lung cancer.Conclusion: The present study demonstrated that XRCC1399 (Gln/Gln), GSTT1, and IL-1RN allele I, I/II served as the risk genotypes. These genes could serve as the biomarkers to predict lung cancer risk. [ABSTRACT FROM AUTHOR]

Oxidative stress, due to reactive oxygen species (ROS) or free radicals, can increase cardiovascular risk factors (CRFs). Lifestyle, environment, and genetics are the primary reasons for ROS generation. The role of genetics in the causation of CRFs mediated by ROS is still elusive. The present study aimed to determine the prevalence of null genotypes of oxidative stress genes (GSTM1 and GSTT1) and cardiovascular risk factors (CRFs) in an urban population. The association of GSTM1 & GSTT1 null genotypes with CRFs was also assessed in this study. A total of 40 participants (permanent residents of Chandigarh, India) were recruited. Anthropometric and physiological data were collected along with blood samples. Biochemical and molecular analysis were performed on all the collected blood samples. More than 90% of the participants had high blood pressure (HBP), 70% had obesity (OBS), and 40% had postprandial hyperglycemia (PPH). The null-genotype of GSTM1 and GSTT1 exhibited 47.50% and 7.50% of participants, respectively. GSTM1 and GSTT1 null genotypes were higher in males than females (50% vs 42.9% and 7.7% vs 7.1%). Agewise distribution showed that the absence of GSTM1 genotype was more in older participants (56.5% vs 35.3%) while GSTT1 genotype was more absent in younger participants (11.8 % vs 4.3%). Participants with null genotypes had trends of high CRFs, but only diastolic blood pressure (DBP) was significantly high. Although, mean arterial pressure (MAP) was also on the verge of significance. Odd ratio analysis showed a 2.383-fold risk of hyperglycemia in participants with either null genotypes. The present study concluded that studied participants are at greater risk of cardiovascular diseases due to high trends of CRFs. High CRFs may be related to the null genotype of GSTM1 and GSTT1 in the urban environment. Further studies with a bigger sample size are warranted to establish the results of the present study. [ABSTRACT FROM AUTHOR]

Background: Important risk factors for the most common sexually transmitted infection (STI) in the world, human papillomavirus (HPV), include early sexual activity, use of contraceptives, tobacco smoking, and immunological and genetic factors. This study aimed to investigate the relationship between GSTM1 and GSTT1 polymorphisms and HPV infection and associated risk factors in a group of women assisted in the public health system of southwestern Paraná, Brazil. Methods and results: A case–control study was designed with 21 women with HPV matched by age in the case group and 84 women without the virus in the control group. Viral detection was conducted via polymerase chain reaction (PCR) and GSTM1 and GSTT1 genotyping by Multiplex PCR. The results showed that the GSTT1 null allele was a protective factor against infection (ORadj 0.219; 95% CI 0.078–0.618; p = 0.004). No relationship was observed for the GSTM1 gene. Smoking was defined as a risk factor (ORadj 3.678; 95% CI 1.111–12.171; p = 0.033), increasing the chances of HPV by up to 3.6 times. Conclusion: This study showed, for the first time, the relationship between GSTM1 and GSTT1 genetic polymorphisms and HPV. We found that this relationship protected women from southern Brazil from viral infection, but not from susceptibility. [ABSTRACT FROM AUTHOR]

Cisplatin is a widely used chemotherapeutic agent. However, its clinical utility is limited because of cisplatin‐induced ototoxicity. Glutathione S‐transferase (GST) was found to play a vital role in reducing cisplatin ototoxicity in mice. Deletion polymorphisms of GSTM1 and GSTT1, members of the GST family, are common in humans and are presumed to be associated with cisplatin‐induced hearing impairment. However, the specific roles of GSTM1 and GSTT1 in cisplatin ototoxicity are not completely clear. Here, under cisplatin treatment, simultaneous deletion of Gstm1 and Gstt1 lead to a more profound hearing loss in CBA/CaJ mice (Gstm1/Gstt1‐DKO) than in wild‐type mice. The Gstm1/Gstt1‐DKO mice, in which phase II detoxification genes were upregulated, exhibited more severe oxidative stress and higher outer hair cell apoptosis in the cochleae than the control mice. Thus, our study revealed that Gstm1 and Gstt1 protect auditory hair cells from cisplatin‐induced ototoxicity in the CBA/CaJ mice, and genetic screening for GSTM1 and GSTT1 polymorphisms could help determine a standard cisplatin dose for cancer patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Amani MT Gusti,1,2 Safaa Y Qusti,1 Suhad M Bahijri,3,4 Eman A Toraih,5,6 Samia Bokhari,7 Sami M Attallah,8,9 Abdulwahab Alzahrani,10 Wafaa MA Alshehri,11 Hawazin Alotaibi,12 Manal S Fawzy13,14 1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Medical Laboratory, Biochemistry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia; 3Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Saudi Diabetes Research Group, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA; 6Department of Histology and Cell Biology (Genetics Unit), Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 7Department of Endocrinology and Diabetes, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia; 8Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 9Department of Clinical Pathology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia; 10Department of Molecular Biology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia; 11Department of Chemistry, Faculty of Science, University of Bisha, Al Namas, Saudi Arabia; 12Ministry of Health, Jeddah, Saudi Arabia; 13Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 14Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi ArabiaCorrespondence: Manal S FawzyDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, EgyptTel + 20 1008584720Fax + 20 64 3216496Email manal_mohamed@med.suez.edu.egBackground: Deregulation of the antioxidant enzymes was implicated in pathogenesis and complications of type 2 diabetes mellitus (T2DM). The data relate the genetic variants of these enzymes to T2DM are inconsistent among various populations.Purpose: We aimed to explore the association of 13 genetic variants of “superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and nitric oxide synthase (NOS)” with T2DM susceptibility and the available clinical laboratory data.Subjects and Methods: A total of 384 individuals were enrolled in this work. Different genotypes of the genes mentioned above were characterized using TaqMan OpenArray Genotyping assays on a Real-Time polymerase chain reaction system.Results: After age- and sex-adjustment, among the studied 13 variants, GSTT1 rs17856199 was associated with T2DM under homozygote (OR=3.42; 95% CI:1.04– 11.2, p=0.031), and recessive (OR=3.57; 95% CI: 1.11– 11.4, p=0.029) comparison models. The NOS2 rs2297518*A allele was more frequent among the T2DM cohort (58.1% vs 35.4%, p< 0.001) and showed a dose-response effect; being heterozygote was associated with higher odds for developing DM (OR=4.06, 95% CI=2.13– 7.73, p< 0.001), whereas being AA homozygote had double the risk (OR=9.06, 95% CI=3.41– 24.1, p< 0.001). Combined NOS2 rs2297518*A and either GSTT1 rs17856199*A or *C genotype carriers were more likely to develop T2DM. Different associations with sex, BMI, hyperglycemia, and/or hyperlipidemia were evident. The principal component analysis revealed NOS2 rs2297518*G, old age, dyslipidemia, high systolic blood pressure, and elevated HbA1c were the main classifiers of T2DM patients.Conclusion: The oxidative stress-related molecular markers, GSTT1 rs17856199 and NOS2 rs2297518 variants were significantly associated with T2DM risk and phenotype in the study population.Keywords: single nucleotide polymorphism, GSTT1, NOS2, oxidative stress, T2DM

Abstract The current study aimed to investigate the relationship between polymorphisms in detoxifying (GSTM1, GSTT1, and GSTP1) genes and their association with colorectal cancer (CRC) in tobacco addicts of Pashtun ethnicity. Polymorphisms in the selected genes were genotyped in a case-control study consisting of 100 histologically confirmed male CRC patients and 100 birth-year and gender-matched healthy controls using the PCR−RFLP method. The GSTM1 null, and GSTT1 null genotypes were significantly contributed to the risk of CRC in the cases (OR= 3.131, 95% CI: 1.451−6.758, P = 0.004, and OR= 3.541, 95% CI: 1.716−7.306, P = 0.001, respectively), whereas the association observed for GSTP1 Val/Val (1.139, 95% CI: 0.356−3.644, P = 0.826) did not show statistical significance. The combined GSTM1 null and GSTT1 null showed a 41-fold increased risk (95% CI: 4.945−351.950, P = 0.001), while, the combined GSTM1 null and GSTP1 Ile/Val or Val/Val variant genotypes exhibited about 3-fold (95% CI: 1.196−7.414, P = 0.019) increased risk to CRC. Similarly, the combined GSTT1 null and GSTP1 Ile/Val or Val/Val variant genotypes showed about a 3-fold (95% CI: 1.285−8.101, P = 0.013) increased risk of CRC. In the combination of three GST genotypes, the GSTM1 null, GSTT1 null, and GSTP1 Ile/Val or Val/Val variant genotypes demonstrated a more than a 22-fold (95% CI: 2.441−212.106, P = 0.006) increased risk of CRC. Our findings suggest that GSTM1 and GSTT1 polymorphism and its combination with GSTP1 may be associated with CRC susceptibility in the Naswar addicted Pashtun population of Khyber Pakhtunkhwa, Pakistan.

Background: The relationship between glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null genotypes (homozygotes for the null alleles) and the susceptibility to age-related macular degeneration (ARMD) have been reported and revealed inconsistent results. Therefore, the current meta-analysis was carried out. Methods: Eligible published articles (before December 2020) were found by searching 8 databases. The data was extracted from articles. The heterogeneity across studies was estimated using Q and I 2 statistics and the odds ratios (ORs) and its 95 % confidence intervals (95 % CI) were estimated. Results: In total, 6 independent studies including 1089 participants (634 controls and 455 patients) were used in the current study. There was no heterogeneity between studies for both polymorphisms. Statistical analysis showed that the null genotypes of the GSTM1 (OR = 1.18, 95 % CI: 0.91 - 1.53, p = 0.191) and GSTT1 (OR = 0.84, 95 % CI: 0.60 - 1.18, p = 0.328) loci were not correlated with the susceptibility to ARMD. Conclusion: The GSTT1 and GSTM1 genetic polymorphisms did not associated with the risk of ARMD in Caucasian populations.

Alemeh Pourkeramati,1 Ehsan Zare Mehrjardi,1 Masoud Dehghan Tezerjani,2 Seyed Morteza Seifati1 1Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran; 2Abortion Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Science, Yazd, IranCorrespondence: Seyed Morteza SeifatiMedical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Yazd, IranTel +98913-1546072Email Seifati@gmail.comBackground: Coronary artery disease (CAD) is a multifactorial disease that may be caused by the interaction between environmental and genetic risk factors. Glutathione S-transferases (GSTs) are known to participate in detoxification and metabolism of a wide range of xenobiotic compounds and oxidative stress products. Considering the interaction between environmental and genetic factors in CAD, we investigated the genetic polymorphisms of GSTM1, GSTT1, and GSTP1 in the Iranian population.Patients and Methods: Two hundred and forty-four CAD cases and 281 healthy controls were studied. The genotype of GSTM1, GSTT1, and GSTP1 genes was determined by multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques. Multivariable logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CI). Multifactor dimensionality reduction (MDR) analysis was also carried out to analyze the gene–gene and gene–environment interaction.Results: The genotype and allele distribution of the three variations were not significantly different between CAD patients and controls (p > 0.05). The subgroup analysis revealed no significant gene–gene interactions or gene–gene combination effects linked to CAD susceptibility. However, MDR analysis selected the GSTM, GSTT pairwise and three genes combination models associated with the susceptibility to CAD. In addition, its result revealed that smoking in combination with GSTM1 (two-way) and GSTT, GSTP (three-way) genes might increase the risk of CAD. Furthermore, a significant interaction between GSTT1-null polymorphism and dyslipidemia was found in multivariable logistic regression analyses in the gene–environmental interactions on CAD risk.Conclusion: Our results suggest that the GSTM1, GSTT1 and GSTP1 genetic variations are not directly associated with the susceptibility to CAD in Iranian patients. Due to MDR results, there might be a non-linear association between interactions of two or three genes and smoking with CAD. There is also an association between CAD risk factors and GST variations, which requires supplementary confirmation with larger sample sizes.Keywords: GSTM1, GSTT1, GSTP1, detoxification system, polymorphisms, coronary artery disease