GSTT1 Genotypes Research Articles

Pharmacogenetic assessment of cytostatic therapy efficacy depending on the polymorphism of T1 and M1 glutathione-S-transferase genes in breast cancer patients

Aim. To study the effect of deletion polymorphism of the GST genes (GSTT1, GSTM1) on chemotherapy (CT) efficacy in women diagnosed with breast cancer (BC) in the Primorsky Krai. Materials and methods. The study involved 132 women with breast cancer aged 23 to 79 years (mean age 48 ± 13 years) who received chemotherapy treatment. The detection of deletion (null) genotypes of GSTM1 and GSTT1 was carried out using multiplex PCR followed by an analysis of the melting curves of the reaction products. Results. Relapse-free survival (RFS) of BC patients with the “null” GSTT1 genotype was statistically significantly higher (116.7 months (9.6 years) versus 75.8 months (6.2 years)) than in patients with the “normal” GSTT genotype. Thus, in the case of the GSTT1“null” genotype, the risk of disease relapse decreased by 2.4 times (HR = 0.418, CI = 0.191–0.915, p = 0.024). Similar to GSTT1, the DFS of patients with the GSTM1 null genotype increased from 72.7 months (6 years) to 76.1 months (6.3 years). At the same time, the risk of disease relapse in carriers of the “null” GSTM1 genotype decreased by 1.7 times (HR = 0.596, CI = 0.369–0.964, p = 0.033) compared with that in carriers of the “normal” GSTM1 genotype. Conclusions. Deletion polymorphism of the GSTT1 and GSTM1 genes has a significant impact on chemotherapy efficacy in breast cancer patients. Carriers of “null” genotypes demonstrated a higher RFS and a lower risk of developing disease relapse. Further research in this direction and validation of the data obtained may contribute to individualizing the treatment of breast cancer patients, optimizing chemotherapy regimens, and reducing the number of adverse events.

The association of combined GSTM1, GSTT1, and GSTP1 genetic polymorphisms with lung cancer risk in male Iraqi Waterpipe Tobacco (Nargila) smokers

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.

Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility

Our study aimed to establish the association of polymorphic variants and disease susceptibility in arsenic-induced metabolic disorders raised due to the variability of arsenic methylation in human population exposed to arsenic in drinking water. Water samples were systematically collected from various regions of Faisalabad, Pakistan, and subjected to arsenic quantification through inductively coupled plasma emission spectrophotometry (ICP-OES). The groundwater exhibited significantly elevated arsenic concentrations (68.18 ± 21.28 μg/L) in comparison to both water and sanitation agency Faisalabad (WASA)-supplied water (9.81 ± 1.2 μg/L) and locally filtered water (8.12 ± 1.42 μg/L), as determined by one-way ANOVA followed by Bonferroni's post-test at P < 0.05. An association was established between arsenic concentration and the incidence of disease, such as diabetes mellitus. A cohort of 120 participants residing in six areas of District Faisalabad was recruited. Urine and blood specimens were collected for analysis. Urine samples underwent ICP-MS analysis in helium collision mode, utilizing germanium as an internal standard. Blood samples were collected for biomarker assessments, including HbA1c, BUN, creatinine, CRP, ALT, AST, GSH, SOD, and MDA, to investigate the evidence of diabetes mellitus. Urinary arsenic concentrations were found to be considerably higher (P < 0.05) in about 22.50 % of the participants, with a mean value of 68.43 ± 16.73 ppb. Biomarker analysis in these participants revealed mean values for BUN (37.19 ± 2.87 mg/dL), creatinine (2.58 ± 0.18 mg/dL), IL-6 (11.35 ± 6.98 pg/mL), CRP (1.90 ± 0.26 mg/dL), MDA (3.70 ± 0.18 nmol/mL), ALT (40.27 ± 5.41 U/L), and AST (38.92 ± 4.72 U/L). Furthermore, the gender-based analysis indicated the higher levels of DMA, MMA, TAs, and TiAs in males compared to females when urine samples were analyzed with HPLC-ICP-MS. Participants with the positive genotype of GSTM exhibited significantly higher levels of TAs, and TiAs concentration in their urine than those with the null genotype of GSTM. Moreover, participants with positive genotypes for GSTT1 and GSTM1 demonstrated elevated levels of DMA in their urine compared to those with genotypes of GSTT1 (−) and GSTM1 (−), although this difference did not attain statistical significance. Participants with the genotype of GSTT1 (+) displayed a considerably higher secondary methylation index than those with genotype of GSTT1 (−). MMA and DMA levels were found to be correlated with the genotypes of GSTT1 and GSTM1 and the amounts of TAs in urine. In conclusion, our findings suggest a linkage between arsenic methylation, particularly levels of DMA and SMI, and GSTT1 and GSTM1 polymorphisms.

Glutathione S Transferase Theta1 and Mu1 (GSTT1 and GSTM1) Deletion Among Autistic Population of India

Introduction: Oxidative stress is an imbalance between an organism's reactive oxygen species (ROS) production and antioxidant defence capacity. Long-term oxidative stress contributes to cellular ageing and plays a role in the pathogenesis of several diseases. Several investigations indicated that oxidative stress has a role in the pathogenesis of ASD. Objectives: Present study was undertaken to record the association of GSTTT1 and GSTM1 null genotype among the autistic population of India. Methods: Genomic DNA was isolated from 108 autistic children along with healthy agematched control. The quality and quantity of the isolated genomic DNA were analysed. GSTT1 and GSTM1 null genotype was analysed using polymerase chain reaction with internal positive control. Statistical analysis was performed using SPSS 15.0. Results: Present study included 85 males and 23 females with a mean age of 11.7 ± 3.5 and 75 males and 33 females with a mean age of 11 ± 2.0 in the control group. 32 (29.6%) autistic cases showed null genotypes for GSTT1 and 21(19.4%) autistic children showed null genotypes for GSTM1. 3 (2.85%) control children showed a null genotype for GSTT1 and 5 (4.6%) control children showed a null genotype for GSTM1. The GSTT1 and GSTM1 null genotypes were observed to be significantly associated with the risk of autism (p value-0.0001, OR-14.73, 95% CI 4.35-49.90) and (p value-0.003, OR-4.731, 95% CI 1.71-13.08) respectively. Conclusion: The findings of our study suggested that GSTT1 and GSTM1 null genotype is one of the potential risk factors for autism through oxidative stress mechanism in our population.

Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population.

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 839: Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer

Abstract Introduction: Recent studies have reported an increased bladder cancer risk with occupational exposure to organic solvents, including exposure to benzene, toluene, and xylene (BTX). The metabolism of solvents is known to be influenced by genetic susceptibility. Here, we evaluated the association between BTX and bladder cancer, stratified by genotype in known bladder cancer susceptibility loci and in variants shown to impact the metabolism of solvents. Methods: We evaluated if single-nucleotide polymorphisms (SNPs) modified the association between BTX exposure and bladder cancer risk in 1182 cases and 1408 controls from a population-based case-control study in New England. Ever and cumulative lifetime exposure to BTX was assessed using occupational histories obtained by personal interviews and exposure-oriented modules in conjunction with a job-exposure matrix. Genotyping was conducted using Illumina arrays and GSTM1 and GSTT1 deletion were determined using melt curve/copy number assays. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between BTX exposure and bladder cancer, stratified by genotype and to calculate p-values for multiplicative interaction. Results: Ever exposure to BTX was more strongly associated with bladder cancer risk among individuals with the GSTT1 null (deletion) genotype (OR 3.53, 95% CI 1.26-9.89), while exposed individuals with the GSTT1 active genotype had a diminished risk (OR 1.40, 95% CI 0.93-2.10, P-interaction = 0.06). The association between benzene exposure and bladder cancer was similarly modified by GSTT1 genotype (carriers of the deletion: OR 5.19, 95% CI 1.91, 14.13; carriers of one or two copies: OR 1.22, 95% CI 0.79, 1.89, p-interaction=0.008). Conclusion: GSTT1 genotype has been shown to impair the metabolism of solvents, particularly for benzene. Here we show that bladder cancer risk is higher among those exposed to solvents who also harbor a common deletion in GSTT1, adding to the evidence of a plausible link between BTX exposures and bladder cancer risk. Citation Format: Deborah Tadesse, Nathaniel Rothman, Shuai Xie, Lauren Hurwitz, Melissa C. Friesen, Dalsu Baris, Molly Schwenn, Alison Johnson, Margaret Karagas, Debra T. Silverman, Stella Koutros. Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 839.

Impact of GSTT1 AND GSTM1 variants and hair mercury concentration in maternal blood pressure among coastal pregnant women in Central Java, Indonesia

The GSTT1 and GSTM1 genes have a role in mercury metabolism and excretion, as well as blood pressure response, impacting birth outcomes. The present study assesses whether GSTT1 and GSTM1 deletion variants and maternal hair Hg concentration are associated with blood pressure and birth outcomes among the Indonesian coastal pregnant mother population. A cross-sectional study was conducted on 139 pregnant women in the Jepara coastal area of Central Java, Indonesia. Maternal characteristics during pregnancy, including blood pressure and birth outcomes, were collected. GSTT1 and GSTM1 gene variants were detected using polymerase chain reaction (PCR). Hair Hg levels were measured using the reducing-vaporization mercury analyzer. The mean maternal hair Hg concentration was 0.727±0.558 μg/g. GSTT1 genotype homozygous deletion was found in 41.7% of subjects, while no GSTM1 deletion was found. No statistically significant difference was found between deletion and non-deletion groups for hair Hg. GSTT1 deletion genotype shows protection but is inconclusive toward diastolic hypertension (p=0.048, OR 0.285, CI 0.077–1.052) and insignificant with birth outcomes (all p>0.05). High hair Hg concentration and positive history of cardiovascular diseases increase the risk of systolic and diastolic hypertension during pregnancy with OR 6.871 (CI 95% 1.445–32.660) and 8.518 (CI 95% 2.126–34.125), respectively, while not in birth outcomes. Maternal Hg exposure and history of cardiovascular diseases are independent risk factors for pregnant hypertension, whereas the GSTT1 homozygous deletion genotype has no role in diastolic hypertension and birth outcomes among the Indonesian coastal pregnant mother population.

Association of Oral Submucous Fibrosis Risk with GSTM1 and GSTT1 Gene Polymorphisms.

To determine the association of GSTM1 and GSTT1 polymorphisms with oral submucous fibrosis (OSF). A case-control study. Place and Duration of the Study: Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore and Oral and Maxillofacial Surgery Department, de Montmorency, College of Dentistry/ Punjab Dental Hospital, Lahore, Pakistan, from 1st April 2019 to 31st April 2020. OSF patients were diagnosed with different clinical staging of mouth opening by Vernier caliper with the help of a professional dentist in the Department of Oral and Maxillofacial, de Montmorency, College of Dentistry, Lahore. One hundred and eight blood samples of OSF patients and 108 samples of normal controls were collected. Genomic DNA was obtained from whole-blood extraction. Multiplex PCR amplification using GSTM1, GSTT1, and β -Globin gene primers was performed. GSTM1 and GSTT1 null genotypes frequencies were found in 43.5% (47/108) and 13.9% (15/108) of controls, whereas 54.6% (59/108) and 25.9% (28/108) of OSF patients, respectively. OSF patients had a greater frequency rate of GSTM1 and GSTT1 null genotypes than controls [OR 1.56, 95% CI 0.91-2.67 (p=0.13)]and [OR 2.17, 95% CI 1.08-4.34 (p=0.04)], respectively. The GSTT1 genotype was found statistically significant with OSF (p=0.05), and risk was also determined. The cumulative effect of null genotypes of GSTM1/GSTT1 did not show any association with the controls and in OSF patients. Proportions of active and null alleles of the patient group were; 86.1%/13.9%; and in control, it was 92.6%/7.4% (OR = 2.01; CI: 0.82-4.97; p=0.18), respectively. The study determined a statistically significant association of GSTT1 gene polymorphism with OSF. Oral submucous fibrosis, GSTM1, GSTT1, Gene polymorphisms, Genetic risk.

Glutathione S-transferase M1, T1, and P1 polymorphisms and periodontitis in a Caucasian population: a case-control study

BackgroundGlutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population.MethodsWe analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr).ResultsThe GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively).ConclusionsThis study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.

Association between null Genotypes of glutathione S-transferase M1 and T1 and susceptibility to systemic lupus erythematosus: A meta-analysis

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.

Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis.

Functional variants of glutathione-S-transferase (GST)-M1, GST-T1, p53 might modulate brain cancer risk by altering the rate of metabolism and clearance of carcinogens from the brain tissue. In this study, the role of GST-M1, GST-T1, p53 polymorphisms on brain tumor was investigated. Brain tumor tissues of 143 patients were obtained from the Gulhane Training and Research Hospital, Department of Neurosurgery between 2019 and 2020. In the xenobiotic mechanism, the null allele frequency in the GST-T1, GST-M1 gene regions of Phase II enzymes by qPCR method were investigated. Single nucleotide polymorphism encoding Arg/Pro conversion in the p53 gene region was analyzed in 120 cases by sequence analysis method. The data were analyzed statistically with patient's demographic and clinical data. GST-M1, GST-T1, p53 genotypes of the patient group were determined. The most frequent genotype was null genotype (0/0) for GST-M1 (χ2 = 39.756, p < 0.001). GST-M1 genotype frequencies were 30.8%, 23.1%, 44.3% for 1/1, 1/0, 0/0, respectively. The most frequent genotype was GST-T1 1/1 following by GST-T1 1/0 (χ2 = 0.335, p = 0.846). GST-T1 genotype frequencies were 64.3%, 30.8%, 4.9% for 1/1, 1/0, 0/0, respectively. GST-M1 null genotype might be associated with the development of brain tumors. Genotype distribution obtained in p53 exon 4 codon 72; Arg/Arg was determined as 31 (25.8%), Arg/Pro 70 (58.3%), and Pro/Pro 19 (15.8%) in the case group, while there were 18 (38.3%), 23 (48.9%), and 6 (12.8%) respectively in the control group. However, the genotype distribution of p53 exon 4 codon 72 among tumorous tissue did not significantly vary from healthy control tissues (χ²=2.536, p = 0.281). The null allele frequency encountered in the GST-M1, GST-T1 gene regions is consistent with the rates in the gene pool called Caucasian in the literature. GST-M1 gene polymorphism may play a crucial role in brain carcinogenesis in Turkish patients. This study based on clinical data is thought to help to understand the important epidemiological features of brain tumors.

Anti-GSTT1 antibodies and Null genotype correlate with histological changes of antibody mediated rejection in kidney transplantation

BackgroundThe presence of anti-Glutathione S-transferase T1 (GSTT1) antibodies (abs) has been hypothesized as a pathogenic contributor in antibody-mediated rejection (AMR). MethodsWe aimed to evaluate the relationship between genetic variants of GSTT1, anti-GSTT1 abs and AMR in a cohort of 87 kidney transplant (KTx) patients using Immucor's non-HLA Luminex assay. Patients were classified according to biopsy-proven AMR and HLA-DSA status: AMR with positive anti-HLA-DSAs (AMR/DSA+, n = 29), AMR but no detectable anti-HLA-DSAs (AMR/DSA-, n = 28) and control patients with stable allograft function and no evidence of rejection (n = 30). ResultsAt an MFI cut-off of 3000, the overall prevalence of anti-GSTT1 abs was 18.3%. The proportion of patients with anti-GSTT1 abs was higher in the AMR/DSA- group (25%), compared to the control (13.3%) and AMR/DSA+ group (3.4%) (p = 0.06). Among patients with anti-GSTT1 abs, the MFI was higher in AMR/DSA- and GSTT1-Null patients. Of 81 patients who underwent GSTT1 genotyping, 19.8% were homozygotes for the null allele (GSTT1-Null). GSTT1-Null status in the transplant recipients was associated with the development of anti-GSTT1 abs (OR, 4.49; 95%CI, 1.2–16.7). In addition, GSTT1-Null genotype (OR 26.01; 95%CI, 1.63–404) and anti-GSTT1 ab positivity (OR 14.8; 95%CI, 1.1–190) were associated with AMR. Within AMR/DSA- patients, the presence of anti-GSTT1 abs didn't confer a higher risk of failure within the study observation period. ConclusionThe presence of anti-GSTT1 abs and GSTT1-Null genotype is associated with AMR, but do not appear to lead to accelerated graft injury in this cohort of early allograft injury changes, with a limited period of follow-up.

Chronic exposure to electronic waste poses risk to liver toxicity with molecular interaction of GSTM1, GSTT1 null variants, and GSTP1

Chronic exposure to electronic waste (e-waste) is becoming a serious concern for health among individuals exposed to it. E-waste has been reported to contain heavy metals, trace elements, and persistent organic pollutants which can trigger health issues through different biological pathways. The liver is a major metabolic and detoxifying organ in the body. Glutathione S-transferase (GST) is a liver enzyme for phase II detoxification that catalyzes glutathione (GSH) conjugation with environmental pollutants. This research aimed to investigate the liver toxicity caused by long-term exposure to e-wastes, exploring the potential association with null variants of GSTT1 and GSTMI, as well as GSTP1. The study was designed as a cross-sectional investigation, in which 256 adult males who were chronically exposed to e-waste and 200 non-exposed control participants, matched for age and gender, were recruited randomly. Standard colorimetric and enzymatic methods were used to analyze biochemical parameters such as serum alkaline phosphatase (ALP), alanine transaminase (ALT), total bilirubin (T. Bil), albumin, and reduced glutathione. Genotypic analysis of the null variant GSTM1, GSTT1, and GSTP1 genes was conducted by standard molecular methods. The study findings indicated a notable surge in ALP, ALT, and albumin levels while T. Bil and GSH levels showed a reduction, suggesting a potential risk of liver toxicity. Additionally, analysis of GSTM1, GSTT1, and GSTP1 genotypes revealed a possible association with GSH levels and the hepatotoxicity risk. The study concluded that the individuals exposed to e-waste exhibited dysregulation of liver enzymes that results in liver toxicity. Moreover, analysis of GSTM1, GSTT1, and GSTP1 at a molecular level revealed that these genes could potentially serve as risk factors for liver toxicity in e-waste chronic exposure.

GSTs genetic polymorphism, gene-environment interaction and association with gallbladder cancer risk in North Indian population: A case-controlled study.

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. 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. 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). 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.

Absence of GSTT1 and polymorphisms in GSTP1 and TP53 are associated with the incidence of acne vulgaris.

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. 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. 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. 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.

Genetic polymorphisms in phase II metabolizing enzymes in alcoholic and idiopathic chronic pancreatitis: Indian scenario.

To study polymorphisms in glutathione-S-transferases (GST-T1, GST-M1, GST-P1) and uridine-5'-diphosphate-glucuronosyl-transferases (UGT1A7) genes and the risk of developing chronic pancreatitis (CP) associated with these polymorphisms. This study included 49 alcoholic and 51 idiopathic chronic pancreatitis patients, 50 alcohol addicts and 50 healthy controls. Polymorphism(s) in GST-T1 and GST-M1 genes were assessed by multiplex polymerase chain reaction (PCR), while PCR-radiofrequency lesioning (RFLP) was employed to assess the same in GST-P1 and UGT1A7 genes. The differences in polymorphism frequency between groups and the risk of developing pancreatitis were assessed by the odds ratio. Strong association of the null genotype of GST-T1 with CP susceptibility was observed. Alcoholics with the Val allele of GST-P1 have higher chances of having pancreatitis. Idiopathic pancreatitis patients with higher age at the onset of pain were found to have the null genotype of GST-M1. Alcoholics with the null genotype of the GST-T1 gene and the Valine allele of the GST-P1 gene are at a higher risk of developing CP. Thus, genotyping of these genes may serve as an important screening tool for the identification of high-risk groups among alcoholics.

Association of NAT2, GSTT1, and GSTM1 gene polymorphisms withprostate cancer risk in Bangladeshi population

One of the leading causes of cancer-related mortality in males is prostate cancer. The latest molecular studies revealed the interconnection of genetic polymorphism of N acetyltransferase (NAT) and Glutathione-S-transferase (GST) gene in the genesis of prostate cancer. The study’s aim was to find out the association of NAT2, GSTT1, and GSTM1 gene polymorphisms with the risk of prostate cancer in the Bangladeshi population. This case-control study included 207 histopathologically diagnosed cases of prostate cancer and 200 age-matched healthy controls. After taking informed written consent, 5.0 mL of venous blood was collected to extract genomic DNA for genetic analysis of NAT2, GSTT1& GSTM1 by PCR-RFLP by multiplex PCR methods. In this study, the mean ± SD age of cases and control was 67.3 ± 8.3, and 62.2 ± 6.8 years, respectively. A higher frequency of mutant NAT2*5A, NAT2*6A, and NAT2*7A in prostate cancer cases was observed in this study, in comparison to controls. Prostate cancer risk was found considerably increased in patients with NAT2 slow genotypes, GSTT1 and GSTM1 null genotypes, compared to control. Furthermore, Prostate cancer risk was found very significantly associated with the presence of combined genotypes that included NAT2 (slow), GSTT1 (null), and GSTM1 (null), and the risk rose 9.64-fold when compared to the wild genotype for NAT2, GSTT1, and GSTM1. Again, it was observed that individuals with positive smoking history/family history of cancer along with NAT2 slow genotype had significantly increased risk for prostate cancer. Moreover, the likelihood of developing a moderate to a high-grade tumor (Gleason score 7), as well as locally progressed or metastatic prostate cancer was considerably greater in persons with NAT2 slow genotypes, GSTT1, and GSTM1 null genotypes. This study established the association of genetic polymorphisms of NAT2, GSTT1, and GSTM1 genes with prostate cancer risk in the Bangladeshi population.

Associations Between Dietary Vitamin C, Serum Ascorbic Acid, and GSTT1 Genotype and Premenstrual Symptoms

Objective Premenstrual symptoms are a cyclically occurring combination of adverse psychological and somatic symptoms that impact the quality of life for most females of childbearing age. Growing evidence suggests that diet may attenuate premenstrual symptoms; however, the relationship between vitamin C and premenstrual symptoms remains unclear. The aim of the research was to determine the association between different measures of vitamin C status and premenstrual symptoms. Method Females (n = 555) aged 20 to 29 years from the Toronto Nutrigenomics and Health Study completed a General Health and Lifestyle Questionnaire, capturing 15 premenstrual symptoms. Dietary intake was measured using a 196-item Toronto-modified Harvard food frequency questionnaire. Serum ascorbic acid concentrations were measured, and participants were categorized into deficient (<11 µmol/L), suboptimal (11–28 µmol/L), and adequate (>28 µmol/L) ascorbic acid levels. DNA was genotyped for the GSTT1 (Ins/Del) polymorphism. Using logistic regression, odds of experiencing premenstrual symptoms were compared between vitamin C intake levels above and below the recommended daily allowance (75 mg/d) between ascorbic acid levels and between GSTT1 genotypes. Results Increased vitamin C intake was associated with premenstrual appetite changes (OR, 1.65; 95% CI, 1.01–2.68). Compared to deficient ascorbic acid levels, suboptimal levels were associated with premenstrual appetite changes (OR, 2.59; 95% CI, 1.02–6.58) and bloating/swelling (OR, 3.00; 95% CI, 1.09–8.22). Adequate serum ascorbic acid levels were not associated with premenstrual appetite changes (OR, 1.69; 95% CI, 0.73–3.94) or bloating/swelling (OR, 1.92; 95% CI, 0.79–4.67). Those with the GSTT1 functional variant (Ins*Ins) had an increased risk of premenstrual bloating/swelling (OR, 1.96; 95% CI, 1.10–3.48); however, the interaction between vitamin C intake and GSTT1 was not significant for any premenstrual symptoms. Conclusions Our findings suggest that indicators of higher vitamin C status are associated with increased premenstrual appetite changes and bloating/swelling. The observed associations with GSTT1 genotype suggest that these observations are not likely due to reverse causation.

Interaction of glutathione S- transferase M1 and T1 gene polymorphism and oxidative stress associated biomarkers (GSH and GST) in pesticide exposed workers in Himachal Pradesh

Humans get oxidative stress as a result of using several pesticides and herbicides in excess. Occupational and environmental exposures harm the public’s health even if their effectiveness has led to their widespread use. The current study’s goal was to assess the activity of the antioxidants glutathione reductase and glutathione S-transferase in a group of HP, India residents who had been exposed to pesticides. Pesticide exposed individuals had their glutathione transferase (GSTM1 and GSTT1) genetic polymorphisms investigated to check for any connections to oxidative stress and toxicity. For the genotyping of GSTM1, GSTT1, and antioxidant enzymatic assays such as GSH and GST, 5 ml of blood was drawn from the population under study. Antioxidant enzymatic activity of GSH (205.63 ± 42.42) and GST (1.65 ± 0.39) were decreased in pesticide exposed group as compared to unexposed group GSH (273.76 ± 56.70) and GST (2.40 ± 0.81). We observed non-significant (p&gt;0.05) results for the association of GSTM1 with GSH and GST enzyme activity as well as similar result have been observed for the association of GSTT1 with GSH and GST activity in the studied population. According to the study, prolonged pesticide exposure results in oxidative stress, which is connected to the necessary genetic variance. The findings may pave the way for further investigation into the toxicogenetics and health impacts of pesticides.

Recent updates on analysis of alteration of Zn level in cancer patients

Zn micronutrient is involved in many physiological processes that include enzyme activity, genomic stability, DNA repairing, apoptosis, immunity, neurological function, response to oxidative stress, and cell signaling. The deficiency of trace element Zn may be responsible for the mutation of DNA, tumor genesis, and carcinoma cell production. The Zn level has been found to decrease in cancer patients as compared to the healthy controls. Various cancer such as breast, ovarian, prostate, lung, Ewing, endometrial, brain, and bladder cancer have been correlated with Zinc deficiency. The polymorphism may be correlated with the ZINC deficiency in several cancer patients. The polymorphism has been observed in MT2A, Matrix metalloproteinase (MMP)-1, MMP-2, MMP-7, and MMP-13 genes significantly change in the Zn levels in the serum of prostate cancer patients. The genotypes GSTM1 and GSTT1 significantly change the concentration of zinc concentration in lung cancer patients. The presence of polymorphism rs1805502 in the GRIN2B gene within the brain is associated with a notably reduced concentration of zinc in the serum. The results of these studies associated with deficiency of zinc in the body may cause DNA damage, mutation in DNA, and tumor growth. This review article provides a detailed description of the deficiency of the Zn element in cancer patients and polymorphisms in genes encoding zinc-dependent proteins associated with different cancers.