GSTT1 Research Articles

GST-Theta1 Enzyme Expression Levels in Brain Tumor and Their Relationship with the Clinical Data of the Patients

The most important drug metabolizing enzyme of the detoxification mechanism is known as Glutathione S-Transferase. GST enzymes may be associated with brain tumor epidemiology, clinical and demographic factors. The correlation between parameters such as changes in Glutathione S-transferase Theta1 proteins, tumor localizations, age, gender, alcohol use, smoking, chemotherapeutic/radiotherapeutic treatment status in normal and brain tumor tissues, diagnosed in neurosurgery department, were examined by immunohistochemistry. GST-Theta1 expressions were analyzed using immunostaining in samples from 149 patients diagnosed with brain tumors between 2016 and 2018. The mean age of the patient group was 49.44 years. 83 (58.45%) patients were male. After immunohistochemical staining, GST-T1 expression was found approximately 9,46 times higher in tumor tissues than in normal tissues (p<0.0001). Tumor tissues from patients who received chemotheraphy showed higher expression of GST-T1 than those who did not (p<0,05). In addition, GST-T1 expression level was observed at a significantly higher level in patients younger than 60 years of age compared to patients over 60 years (p<0.026; p<0.05). There was no statistically significant relationship between patients smoking behaviors, alcohol consumption, tumor localization and GST-T1 expressions. It is aimed to determine the GST-T1 protein expressions and to contribute to the examination of epidemiological and prognostic factors of brain tumors by comparing them with demographic and clinical data.

Genotoxicity biomarkers in car repair workers from Barranquilla, a Colombian Caribbean City

ABSTRACT Exposure to chemicals and particles generated in automotive repair shops is a common and underestimated problem. The objective of this study was to assess the genotoxic status of auto repair workers with (1) a questionnaire to gather sociodemographic information and self-reported exposure to hazardous chemicals and (2) measurement of various biochemical parameters. Blood and oral mucosa samples were collected from 174 male volunteers from Barranquilla, Colombia, aged 18–55 years: 87 were active car repairmen and 87 were individuals with no known exposure to hazardous chemicals. Peripheral blood lymphocytes were collected for the comet and cytokinesis-blocking micronucleus (CBMN) assays, while oral mucosal epithelium extracted to quantify micronucleated cells (MNC). DNA was extracted to assess polymorphisms in the DNA repair (XRCC1) and metabolism-related genes (GSTT1 and GSTM1) using PCR-RFLP. DNA damage and frequency of micronuclei (MN) in lymphocytes and oral mucosa were significantly higher in exposed compared to control group. In both groups genotypes and allelic variants for XRCC1 and GSTT1 met the Hardy-Weinberg equilibrium (HWE). In contrast, GSTM1 deviated from HWE. In the exposed group genotypic variants were not correlated with DNA damage or MN presence in cells. DNA damage and occurrence of MN in mucosa and lymphocytes correlated with age and time of service (occupational exposure ≥ 3 years). In summary, workers in car repair shops exhibited genotoxic effects depending upon exposure duration in the workplace which occurred independent of DNA repair XRCC1 gene and metabolism genes GSTT1 and GSTM1. Date demonstrate that health authorities improve air quality in auto repair facilities to avoid occupational DNA damage.

CLINICAL AND GENETIC DETERMINANTS OF PERINATAL PATHOLOGY IN NEWBORNS

One of the pressing issues of healthcare nowadays is applying methods of molecular genetics aimed at identifying and assessing genetic risk factors and early diagnosis of perinatal pathology. Numerous studies have contributed to identifying risk factors that affect the health of newborns. The aim of this work is to investigate the associations between the development of perinatal pathology in premature and full-term infants with polymorphism of genes of the glutathione transferase family (GSTT1, GSTM1, GSTP1), renin-angiotensin system (ACE, AGT2R1). Materials and methods. The study included 110 full-term infants with asphyxia, 30 healthy full-term infants for the control group, and 125 preterm infants with perinatal infections, 21 preterm infants with broncho-pulmonary dysplasia, and 70 conditionally healthy preterm infants. A set of routine clinical and laboratory methods of research and determining gene polymorphism was performed. Results. The presence of a non-functional allele of the GSTT1 gene and DD variant of the ACE gene in newborns is associated with the development of severe perinatal asphyxia (p = 0.006 and p = 0.003, respectively). Children with GSTT1 "-" and AC AG2TR1 genotypes have significantly higher levels of diastolic pressure in the first day after birth than children with functional genotypes of these genes (p <0.05). The median mean duration of mechanical ventilation and CPAP in children with GSTT1 genotype "-" was significantly higher than that in children with GSTT1 genotype "+" (p = 0.01 and p = 0.001, respectively). Conclusion. Polymorphism studies of glutathione transferase and renin-angiotensin genes can be used to predict the severity of a child's condition after birth.

Evaluation of molecular markers GSTM1 and GSTT1 and clinical factors in breast cancer: case-control study and literature review

The study was conducted to evaluate the frequency of polymorphisms in GSTM1 and GSTT1 genes in patients with breast cancer compared with individuals without history of cancer, and the association of these polymorphisms with clinical/epidemiological parameters. There were evaluated 752 women (219 patients and 533 controls). Molecular analysis was performed by the Polymerase Chain Reaction (PCR). Statistical analysis was used multiple logistic regression and descriptive statistics. Age ≥ 50 years (OR = 3.22, 95% CI = 2.30–4.51, p < 0.001) and alcohol consumption (OR = 1.60, 95% CI = 1.13–2.27, p = 0.008) were associated to the development of breast cancer, while smoking and null genotypes GSTM1 and GSTT1 presented no association. GSTM1 and GSTT1 polymorphisms presented no relationship with the clinical and histopathological parameters or molecular subtypes of breast cancer. Ninety-two percent of tumours were invasive ductal, 66% were grade II, 65% were larger than 2 cm, the stages II (35.3%) and III (31.2%) were the most prevalent, and 47.7% were molecular subtype luminal B. Individuals aged ≥ 50 years and alcohol consumers have more chance to developing breast cancer. GSTM1 and GSTT1 polymorphisms are not associated to the risk of breast cancer.

Bisphenol S leads to cytotoxicity-induced antioxidant responses and oxidative stress in isolated rainbow trout (Oncorhyncus mykiss) hepatocytes.

Bisphenol S (BPS) is a chemical compound that is utilized in the plastic industry as an alternative to bisphenol A (BPA). The toxic effects of BPS in fish is less known and limited. Therefore, in the present study, the influence of BPS on rainbow trout (Oncorhyncus mykiss) hepatocytes in vitro was investigated. For this purpose the fish hepatocytes were isolated, and then the cultured cells were treated with increasing concentrations of BPS (0, 15.63, 31.25, 62.50, 125, 250, and 500 µM) for 24h. The cytotoxic impact of BPS was determined in the culture media using lactate dehydrogenase assay and then, the antioxidant defence indicators were assayed. The results showed that concentration-dependent increases were observed in the percentage of cytotoxicity. The superoxide dismutase activity was reduced, while the catalase and glutathione peroxidase activity increased with all of the BPS concentrations. The glutathione S-transferase (GST) activity significantly increased after a BPS concentration of 31.25 µM or higher, while GST Theta 1-1 activity was decreased by the same concentrations of BPS. The reduced glutathione content significantly decreased with a BPS concentration of 31.25 µM or higher, and the malondialdehyde content increased after BPS concentrations of 125, 250, and 500 µM. The findings determined herein suggested that BPS causes cytotoxicity in fish hepatocytes and can lead to oxidative stress, resulting hepatotoxic in fish. Thus, the utilization of BPS instead of BPA as safe alternative in industry should be re-evaluated in the future for environmental health.

Cytokinesis-block micronucleus cytome (CBMN-CYT) assay and its relationship with genetic polymorphisms in welders

Fumes generated in the welding process are composed of micrometric and nanometric particles that form when metal fumes condense. The International Agency for Research on Cancer established that many compounds derived from the welding process are carcinogenic to humans. Still, there are few studies related to the role of genetic polymorphisms. This work aimed to analyze the influence of OGG1 Ser326Cys, XRCC1 Arg280His, XRCC1 Arg194Thr, XRCC1 Arg399Gln, XRCC3 Thr241Met, GSTM1, and GSTT1 gene polymorphisms on DNA damage of 98 subjects occupationally exposed to welding fumes and 100 non exposed individuals. The results showed that individuals exposed to welding fumes with XRCC3 Thr241Thr, XRCC3 Thr241Met, and GSTM1 null genotypes demonstrated a significantly higher micronucleus frequency in lymphocytes. In contrast, individuals with XRCC1 Arg399Gln and XRCC1 Gln399Gln genotypes had significant levels of NPBs. OGG1 326 Ser/Cys, OGG1 326 Cys/Cys, XRCC1 194Arg/Thr, XRCC1 194Thr/Thr, and GSTT1 null genotypes exhibited significantly higher apoptotic values. Also, XRCC1 194Arg/Trp, XRCC1 194Thr/Thr, and GSTM1 null genotype carriers had higher necrotic levels compared to XRCC1 194Arg/Arg and GSTM1 nonnull carriers. Compositional analysis revealed the presence of iron, manganese, silicon as well as particles smaller than 2 μm that adhere to each other and form agglomerates. These results may be associated with a mixture of components, such as nitrogen dioxide, carbon monoxide, and metallic fumes, leading to significant DNA damage and cell death processes. These findings demonstrated the importance of the association between individual susceptibility and DNA damage levels due to occupational exposure to welding fumes; and constitute one of the first studies carried out in exposed workers from Colombia.

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

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

The Cumulative Effect of Gene-Gene Interactions Between GSTM1, CHRNA3, CHRNA5 and SOD3 Gene Polymorphisms Combined with Smoking on COPD Risk.

BackgroundChronic obstructive pulmonary disease (COPD) is a multifactorial disorder which is affected by external and internal risk factors. People with no external risk factors may be significantly affected and develop pulmonary disease. The study aimed to define gene–gene and gene–environmental effects on COPD.MethodsA case control study involved 181 COPD patients and 292 healthy individuals, with peripheral blood sampling and adequate questionnaires. Genotyping was done with various types of PCR design for GSTM1 (null del), GSTT1 (null del), EPHX1 (rs2234922 and rs1051740), GSTP1 (rs1695 and rs1138272), CHRNA3 (rs1051730 and rs12914385), CHRNA5 (rs16969968 and rs17486278), and SOD3 (rs1799895 and rs699473) gene polymorphisms. Gene–gene and gene–environmental interactions were investigated using multidimensional regression analysis.ResultsFrequency of risk alleles of rs1051730 (p = 0.001), rs16969968 (p <0.001), and rs1799895 (p <0.001) polymorphisms were significant in univariate analysis. For gene–gene interaction, GSTM1 null, rs1051730, rs16969968, and rs1799895 polymorphisms independently contributed to risk of COPD and any combinations of the risk genotypes have a higher risk of disease. A cumulative effect of the four risk polymorphisms increased the risk of COPD for the smoking index (cOR = 13.6, p <0.001), cigarettes per day (cOR = 32.08, p <0.01), nicotine dependence (cOR = 12.0, p <0.01), and smoking status (cOR = 17.02, p <0.01) for gene–environmental interaction.ConclusionSeveral pivotal genes showed distinct effects for COPD, and some synergistic effects affected the disease progression. The development of COPD was synergistically increased with gene–gene and gene–environmental risk factors.

Up-regulation of GSTT1 in serous ovarian cancer associated with resistance to TAXOL / carboplatin

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.

Glutathione S-transferase gene polymorphisms in association with susceptibility to lead toxicity in lead- and cadmium-exposed children near an abandoned lead-zinc mining area in Kabwe, Zambia.

Interindividual genetic variations determine human's susceptibility to heavy metal-induced toxicity. Thus, we analyzed blood concentrations of lead (Pb) and cadmium (Cd) in 140 lead-exposed children. Genotyping of the glutathione S-transferase (GST) genes, GSTM1, GSTT1, and GSTP1 genes, was carried out to investigate their possible association with heavy metal concentrations and the risk of susceptibility to Pb toxicity. Exposure to both heavy metals was prevalent among the children. The blood Pb level ranged from 3.30 to 74.0 μg dL-1 with an average value of 26.8 μg dL-1 that is five times above its reference level. The average Cd level (0.22 μg L-1) was below its reference level. The metal-gene interaction showed positive correlation between GSTT1 null genotype and Pb and Cd levels (β = 0.11; p = 0.02 and β = 0.10; p = 0.01, respectively). More pronounced effects (β = 0.19; p < 0.01 and β = 0.25; p = 0.04) were found for the mixture of the three putative genes with blood Pb concentration. The susceptibility analysis using 10 μg dL-1 as blood Pb cutoff level showed a high risk of Pb toxicity (OR = 2.54; 95% CI: 1.02-6.32, p = 0.04) for children carrying the GSTP1 Ile/Val genotype. Further, the combined effect of GSTP1 Ile/Val with GSTT1 null genotype was more pronounced and showed an increased risk of susceptibility to Pb toxicity (OR = 11.7; 95% CI: 1.36-102.1, p = 0.02). In summary, this study suggests that GSTT1 null and GSTP1 Ile/Val genotypes are the main genetic factors, and individual and specific combinations of GSTP1 Ile/Val with GSTM1 and GSTT1 GST polymorphisms are associated with susceptibility to Pb toxicity.

Homozygous deletion of glutathione S-transferase theta 1 and mu 1 increase the risk of non-syndromic oral clefts in a Mexican population

ObjectiveTo investigate whether null variants of Glutathione S-transferase Mu 1 (GSTM1) and GST Theta 1 (GSTT1) in infants and mothers, as well as maternal exposures to environmental factors, contribute to the risk of non-syndromic cleft lip with or without palate (NSCL/P) in a Mexican population. DesignWe performed a matched pair case-control study, including 98 cases and 98 controls and their mothers. Sociodemographic information and environmental exposures were collected by a questionnaire. Null variants of GSTM1 and GSTT1 were assessed by multiplex Polymerase Chain Reaction (PCR). Odds ratios (OR) and their 95 % confidence intervals (CI) were calculated to estimate risks. The interaction of genetic variables with smoking and adjusted ORs were evaluated by binary logistic regression. ResultsHomozygous null GSTM1 was associated with the risk of NSCL/P when present in mothers (OR = 2.45, 95 % CI 1.23–4.86) or infants (OR = 2.98, 95 % CI 1.45–6.14). A higher risk was also found when children carried the homozygous null GSTT1 (OR = 4.89, 95 % CI 2.42–9.87). In mothers, this variant showed a crude risk of 9.17 (95 % CI 3.95–21.29), which increased to OR = 13.81 (95 % CI 1.63–117.09) upon interaction with frequent passive smoking (5–7 days/week). Sociodemographic and other environmental exposures were not significantly associated with the risk of NSCL/P. ConclusionsMaternal and infant GSTT1 and GSTM1 homozygous null genotypes were associated with a higher risk of NSCL/P, and the results suggest an interaction of the maternal GSTT1-null/null genotype with frequent passive smoking.

Effects of Dietary Supplementation of Algae-Derived Polysaccharides on Morphology, Tight Junctions, Antioxidant Capacity and Immune Response of Duodenum in Broilers under Heat Stress.

Simple SummaryHeat stress (HS) has become a great challenge for poultry production in tropical and subtropical regions. HS results in the intestinal dysfunction of broilers, which seriously affects their productivity. Our previous study suggested that dietary supplementation of algae-derived polysaccharides (ADP) could promote the intestinal barrier function in broilers, but the effect of dietary ADP supplementation on the intestinal health of broilers under HS remains unclear. The present study showed that dietary ADP supplementation improved the duodenal tight junction expression of broilers under HS, and found that dietary ADP mitigated HS-induced oxidative stress and inflammation response by regulating Nrf2 and NF-κB signaling pathways. These findings reveal the potential application of ADP as an HS-alleviating agent to maintain gut health in broilers.To evaluate the ameliorative effect of algae-derived polysaccharide (ADP) supplementation on duodenal injury caused by heat stress (HS) in broilers, a total of 144 male yellow-feathered broilers (56-day-old) were randomly allocated into three groups: The TN group (thermoneutral zone, broilers were raised at 23.6 ± 1.8 °C); HS group (heat stress, broilers were exposed to 33.2 ± 1.5 °C 10 h/day, 8:00 a.m.–18:00 p.m., the temperature in the remaining period was consistent with the TN group); HSA group (heat-stressed broilers were fed with ADP supplemented diet at 1000 mg/kg). There were six replications in each treatment, and eight broilers in each replication. The feeding trial lasted four weeks. The results showed that dietary ADP supplementation tended to increase the villus height (p = 0.077) and villus width (p = 0.062), and decrease the apoptosis rate (p = 0.081) in the duodenum of broilers under HS. Furthermore, dietary ADP increased the relative mRNA and protein (based on immunofluorescence) expression levels of occludin and zonula occludens-1 (ZO-1) in the duodenum of broilers under HS (p < 0.05). In addition, dietary ADP enhanced the total antioxidation capacity (T-AOC) and activity of glutathione-S transferase (GST), while reducing the malondialdehyde (MDA) concentration of the duodenum in broilers under HS (p < 0.05). Moreover, dietary ADP supplementation upregulated the duodenal nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase 1 (GPx1) and glutathione S-transferase theta 1 (GSTT1) mRNA expression levels in heat-stressed broilers (p < 0.05). Furthermore, compared with the HS group, broilers fed with an ADP supplemented diet had a higher relative mRNA expression of inhibitor kappa B alpha (IκBα) (p < 0.05) and a lower relative mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the duodenum (p < 0.05). In summary, dietary ADP supplementation had an ameliorative effect on HS-induced impairment of tight junctions, antioxidant capacity and the immune response of the duodenum in broilers. These beneficial effects might be related to the modulation of Nrf2 and NF-κB signaling pathways.

The role of occupational factors and individual susceptibility in the development and course of bronchopulmonary diseases

Over the past decades, the world has seen an increase in occupational lung diseases, the leaders being asthma and chronic obstructive pulmonary disease (COPD). The article presents the results of 5-year observation of food industry workers. Clinical functional and molecular genetic studies have been carried out to identify the frequency and severity of asthma and COPD along with the individual predisposition to pulmonary conditions.Methods. 76 people of both sexes with the average age of 43.5 ± 3.6 years were examined on an outpatient basis. All subjects had daily contact with toxic and allergenic aerosols and organo-mineral dust. The respiratory function and the presence of bronchial hyperresponsiveness to occupational factors was assessed by spirography and peak flowmetry in response to exposure and elimination of industrial aerosols. Immunological and molecular genetic tests were performed: identification of hyposecretory alleles of the α1 -АТ gene, determination of polymorphisms of the GSTM1 and GSTT1 genes, immunoglobulin levels (IgE, IgM, IgG) and cytokine status (IL-4, -6, -8; TNF-α).Results. During the 5-year follow-up period, there was a significant increase in the number of employees with severe respiratory symptoms – 36.8% (95% CI – 21.2–36.8; p &lt; 0.05) and a statistically significant decrease in the respiratory function (p &lt; 0.001). Progressive decrease in the respiratory function in healthy individuals and the appearance of new and more severe cases of asthma and COPD were registered primarily among workers with hyposecretory alleles of the α1-АТ gene and/or zero alleles of the glutathioneS-transferase genes (GSTM1 and GSTT1) in combination with abnormal cytokine status.Conclusion. Individual risk factors for the development of asthma and COPD in individuals working in contact with toxic and allergenic aerosols and organo-mineral dust are hyposecretory PiMZ variant of the α1-АТ gene and deletions in the glutathione-S-transferase genes (GSTM1 0/0 and GSTT1 0/0) in combination with abnormal cytokine status. Long-term research results suggest the prognostic value of assessing individual sensitivity to industrial aerosols and the development of bronchopulmonary pathology.

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

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

Resequencing 250 Soybean Accessions: New Insights into Genes Associated with Agronomic Traits and Genetic Networks

The limited knowledge of genomic diversity and functional genes associated with the traits of soybean varieties has resulted in slow progress in breeding. In this study, we sequenced the genomes of 250 soybean landraces and cultivars from China, America, and Europe, and investigated their population structure, genetic diversity and architecture, and the selective sweep regions of these accessions. Five novel agronomically important genes were identified, and the effects of functional mutations in respective genes were examined. The candidate genes GSTT1, GL3, and GSTL3 associated with the isoflavone content, CKX3 associated with yield traits, and CYP85A2 associated with both architecture and yield traits were found. The phenotype–gene network analysis revealed that hub nodes play a crucial role in complex phenotypic associations. This study describes novel agronomic trait-associated genes and a complex genetic network, providing a valuable resource for future soybean molecular breeding.

Glutathione-S-transferases genes-promising predictors of hepatic dysfunction.

One of the most commonly known genes involved in chronic diffuse liver diseases pathogenesis are genes that encodes the synthesis of glutathione-S-transferase (GST), known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins, through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products. The group of GST enzymes consists of cytosolic, mitochondrial and microsomal fractions. Recently, eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known: α-, ζ-, θ-, κ-, μ-, π-, σ-, and ω-. The GSTs gene family in the Human Gene Nomenclature Committee, online database recorded over 20 functional genes. The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins. Nevertheless, human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene. Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases, particularly non-alcoholic fatty liver disease, hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma. Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology, and correlations with the natural course of the diseases were subsequently postulated.

A prospective observational study to evaluate Glutathione S-transferase gene polymorphism and its association with Antitubercular drugs induced liver injury in tertiary hospital

BackgroundAnti-TB drugs are most common cause of idiosyncratic hepatotoxicity worldwide. Reactive metabolite formed during drug metabolism has been involved in a clinical toxicity are described as ‘idiosyncratic’ drug induce liver injury (DILI). We have observed the distribution of glutathione S -transferase (GST) gene polymorphism & its association with drug-induced liver injury in patients taking anti-tubercular treatment. MethodsA prospective observational study including 96 patients receiving anti-tubercular treatment. Blood sample was collected for LFT and gene extraction after ruling out other cause of liver injury. DNA extraction for GST gene was done follow by polymerase chain reaction to identify homozygous null mutation at GSTM1 and GSTT1 loci. Association of GSTM1 and GSTT1 gene with DILI was seen. ResultsOut of 96 tubercular patients under treatment, drug induced liver injury was found in 21 (21.9%) patients and 75 does not develop DILI, GST M1 gene null mutation was observed in 14 (66.7%), GST T1 gene null mutation was observed in 9 (42.9%), Both GST gene null mutation was observed in 8 (38.1%) in DILI group. ConclusionThe GSTM1 gene null mutation and both GSTM1 and T1 gene null mutation were a risk factor for the development of DILI. But there is no significant association between GSTT1 gene null mutation and DILI in TB patients.

Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome.

Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS‐CoV‐2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione‐S‐transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID‐19 susceptibility, as well as its outcome. The study included 269 RT‐PCR confirmed COVID‐19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1−/−, GSTT1−/− and GSTM1−/−/GSTT1−/− was higher in severe COVID‐19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28‐fold higher in patients with the GSTT1−/− genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1−/− genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID‐19 patients with the GSTT1−/− genotype showed higher mortality.

CYTOGENETIC CONSEQUENCES OF THE MIXED EFFECTS OF OPISTORCHIASIS AND TICK-BORNED ENCEPHALITIS IN ASSOCIATION WITH POLYMORPHISM BY GLUTHATHIONE-S-TRANSFERASE GENES

Purpose: to study the duration of the preservation of the cytogenetic effects of tickborne encephalitis (TBE) in individuals infected with the Opisthorchis felineus (OF) helminth, which differ in alleles of the glutathione-S-transferase enzyme genes. Methods: the objects of the study were patients with tick-borne encephalitis in whom the frequencies of micronucleated lymphocytes were detected. All examined patients were subdivided into two groups: TBE patients non-infected with OF, and TBE patients infected with OF. Multiplex PCR was used to analyze the GSTM1 and GSTT1 genes. Results: patients with TBE, infected with OF, had a significantly lower increase in the level of cytogenetic disorders than patients with TBE without OF infection; at the same time, the restoration of the cytogenetic norm in this group was not reached, and there was no association between the frequency of micronucleated lymphocytes and different variants of the glutathione-S-transferase enzyme genes. Conclusion: the frequency of cytogenetic changes in TBE patients infected with OF are significantly less than one in patients with TBE without OF infection. Polymorphism in the genes of the enzyme glutathione-S-transferase does not have significant effect on the cytogenetic disorders in patients with TBE with OF infection.

Physiological and Molecular Study for Some Cases of Coronary Artery Disease

Coronary artery diseases (CAD) known as the disorders of the heart and the blood vessels, which claimed 17.1 million lives a year worldwide. to identify the correlation between the coronary artery disease and some physiological and molecular parameters in men. one hundred blood samples (5 ml) collected from coronary artery diseases patients, the Complete blood count parameters (CBC), Serum concentrations of Creatinine, Glucose, Cholesterol, Triglycerides, HDLLDL, T3 , T4 and TSH were measured in current study. Multiplex polymerase chain reaction used to determine the presence or absence of GSTM1 and GSTT1 genes in the genomic DNA and CYP1A1 as an internal control. The results of current study showed significant increase in the total WBC, Neutrophil, Lymphocyte, MCH, MCHC,PLT, MPV, PCT, creatinine, glucose, cholesterol, Triglyceride, LDL andTSH in patients group when compared with control.The percentage of coronary artery diseases were increase 47% when the GSTM1 gene absence in patients group compared with control,while no significant differences were recorded when GSTT1 gene absence and the two genes absence in patient group compared with control.The study concluded that physiological indicators may increase in patients with Coronary artery diseases .