GST gene polymorphisms and the risk of colorectal cancer development.

Increasingly often, molecular studies of colorectal cancer focus on low penetrance genes. Among the factors potentially modifying the risk of contracting colorectal cancer is the glutathione S-transferase (GST) gene family, encoding enzymes of the glutathione transferase type. Proteins of the GST family (glutathione S-transferases) are enzymes detoxifying a wide range of hazardous substances, such as reactive oxygen species (ROS) or xenobionts. Thus, their role, among other things, is the protection of DNA against oxidative damage, which may lead to mutations, and in consequence, favour carcinogenesis. GST gene polymorphisms may affect the functioning of the encoded enzymes, exerting an effect on the level of DNA damage, and therefore may have an indirect influence on the risk of the development of cancer. At present, there are many studies available concerning GST gene polymorphisms as factors modulating the risk of developing cancer, including colorectal cancer.

Glutathione S-Transferase P1 Genetic Variant's Influence on the HbA1c Level in Type Two Diabetic Patients.

GST (glutathione S-transferases) are capable of influencing glucose homeostasis, probably through regulation of the response to oxidant stress. The aim of our study was to investigate the relationship between GSTP1 gene polymorphism and glycated hemoglobin (HbA1c) levels in type two diabetic (T2D) patients. A total of 307 T2D patients were included. Analysis of the GSTP1 gene polymorphism (rs1695) was conducted using the TaqMan qPCR method endpoint genotyping. HbA1c was determined using a COBAS 6000 autoanalyzer. A univariable linear regression and multivariable linear regression model were used to investigate the association between mean HbA1c level and GSTP1 gene polymorphism, age at T2D diagnosis, T2D duration, therapy with insulin, gender, BMI, smoking status. GSTP1 Val/Val genotype, age at T2D diagnosis, T2D duration and therapy with insulin were statistically significant contributors to HbA1c levels (p < 0.05). Multivariable regression analysis revealed that GSTP1 (Val/Val vs. Ile/Ile) was associated with higher HbA1c even after adjustment for variables that showed a statistically significant relationship with HbA1c in univariable analyses (p = 0.024). The results suggest that GSTP polymorphism may be one of the risk factors for higher HbA1c in T2D patients. Our study is limited by the relatively small sample size, cross-sectional design, and lack of inclusion of other oxidative stress-related genetic variants.

Association between Glutathione S-Transferases Gene Variants and COVID-19 Severity in Previously Vaccinated and Unvaccinated Polish Patients with Confirmed SARS-CoV-2 Infection.

As the outcome of COVID-19 is associated with oxidative stress, it is highly probable that polymorphisms of genes related to oxidative stress were associated with susceptibility and severity of COVID-19. The aim of the study was to assess the association of glutathione S-transferases (GSTs) gene polymorphisms with COVID-19 severity in previously vaccinated and unvaccinated Polish patients with confirmed SARS-CoV-2 infection. A total of 92 not vaccinated and 84 vaccinated patients hospitalized due to COVID-19 were included. The WHO COVID-19 Clinical Progression Scale was used to assess COVID-19 severity. GSTs genetic polymorphisms were assessed by appropriate PCR methods. Univariable and multivariable analyses were performed, including logistic regression analysis. GSTP1 Ile/Val genotype was found to be associated with a higher risk of developing a severe form of the disease in the population of vaccinated patients with COVID-19 (OR: 2.75; p = 0.0398). No significant association was observed for any of the assessed GST genotypes with COVID-19 disease severity in unvaccinated patients with COVID-19. In this group of patients, BMI > 25 and serum glucose level > 99 mg% statistically significantly increased the odds towards more severe COVID-19. Our results may contribute to further understanding of risk factors of severe COVID-19 and selecting patients in need of strategies focusing on oxidative stress.

Influence of Algae Supplementation on the Concentration of Glutathione and the Activity of Glutathione Enzymes in the Mice Liver and Kidney.

Algae are potential and natural source of long-chain polyunsaturated fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The diatom Pinnularia borealis accumulates high levels of EPA and may be considered as a source for commercial production of dietary supplements. In this study we asked the question whether diet supplementation with P. borealis may augment antioxidant defense and ameliorate risk factors for cardiovascular diseases. We fed mice (Mus musculus) with lyophilized diatom solutions of different concentrations (1%, 3%, and 5%) for 7 days. Then we measured glutathione content and the activity of glutathione redox system enzymes, total cholesterol and triacylglycerol concentrations, and malondialdehyde concentration in the liver and kidney. We found that cholesterol and triacylglycerol concentrations in the liver and kidneys were the lowest in mice who were fed with the highest concentration of Pinnularia borealis, suggesting protective properties of algae. Additionally, the lowest concentration of Pinnularia borealis was sufficient to improve antioxidant capacity. Our results suggest that P. borealis may be used as a source for dietary supplements rich in EPA, but the amount supplied to the organism should be limited.

Glutathione S-transferases gene polymorphism influence on the age of diabetes type 2 onset.

INTRODUCTION: Type 2 diabetes (T2D) is a multifactorial disease affecting mostly adults older than 40 years. The aim of the study was to examine GST gene polymorphism influence on the risk of T2D, especially in young adults. RESEARCH DESIGN AND METHODS: 200 diabetic patients and 221 healthy controls participated in this study. Three GST gene polymorphism have been analyzed: GSTP1 (single-nucleotide polymorphism Ile105Val), homozygous deletion of GSTT1 (null/null) and GSTM1 (null/null), using TaqMan real-time quantitative PCR. RESULTS: The distribution of examined polymorphisms was similar in patient group and control group. Statistically significant differences were demonstrated for the combination of GSTP1 Val/Val and GSTT1 null/null genotypes between patients diagnosed before 40 years of age and healthy people (12.5% vs 0.9%, p=0.016). Moreover, all three examined gene polymorphism together (GSTP1 Val/Val, GSTM1nul/null and GSTT1 null/null genotype) was observed in 12.5% of patients diagnosed before 40 years of age and in 0.5% of healthy individuals (p=0.013). CONCLUSION: In conclusion, the results suggest that GST polymorphism may be one of the risk factors for developing T2D at a younger age than the T2D population average.

The Influence of Red Meat on Colorectal Cancer Occurrence Is Dependent on the Genetic Polymorphisms of S-Glutathione Transferase Genes.

BACKGROUND: It is postulated that both individual genotype and environmental factors such as diet may modify the risk of developing colorectal cancer (CRC). The influences of GST gene polymorphism and red meat intake on CRC occurrence in the Polish population were analyzed in this study. METHODS: Genotyping was performed with the qPCR method. RESULTS: A high frequency of meat consumption was associated with an over 2-fold increase in the risk of colorectal cancer odds ratio (OR) adjusted for sex and age = 2.4, 95% confidence interval (CI); 1.3-4.4). However, after analyzing the genetic profiles, in the absence of polymorphisms of all three analyzed genes, there was no association between a high frequency of meat consumption and the occurrence of CRC. In the case of GSTM1 gene polymorphism, the high frequency of meat consumption increased the risk of CRC by almost more than 4 times (OR adjusted for sex and age = 3.8, 95% CI: 1.6-9.1). For GSTP1 gene polymorphism, a 3-fold increase in CRC risk was observed with a high frequency of meat consumption (OR adjusted for sex and age = 3.4, 95% CI: 1.4-8.1). In the case of GSTT1 gene polymorphism, the increase in risk of CRC was not statistically significant (OR adjusted for sex and age = 1.9, 95% CI: 0.4-8.5). CONCLUSIONS: The frequency of red meat intake in non-smokers increases the risk of colon cancer in the case of GST gene polymorphisms.

The influence of scopolamine and extreme temperatures on the lipid level in some mouse organs.

OBJECTIVES: The effect of scopolamine administration at dose 0,5 g/kg b.w. and high (+40 degrees C) and low (+4 degrees C) temperature on the level of triacyloglycerides, total lipids and cholesterol in the mouse liver, kidney and muscle of males and females. METHODS: The homogenates of the liver, kidney and muscle were taken for examination. The concentrations of triacyloglycerides, total lipids and cholesterol was estimated according to the Bio-La-Tests (Poland). RESULTS: The concentration of triacyloglycerides and total lipids in the liver, kidney and muscle increased of males and females after scopolamine injections and after exposure to high and low temperatures. CONCLUSION: Scopolamine may effect an increase in the rate of the lipid metabolism.

The effect of melatonin on glutathione and glutathione transferase and glutathione peroxidase activities in the mouse liver and kidney in vivo.

OBJECTIVES: The changes in reduced glutathione (GSH), activity of glutathione transferase (GST) and glutathione peroxidase (GSPx) after administration of exogenous melatonin (N-acetyl-5-methoxy-tryptamine) at a dose 20 mg/kg b.w. were investigated for five and ten days in the liver and kidney of male and female mice. METHODS: The liver and kidney were homogenized in 0.1 M phosphate buffer. Glutathione level and activity of studied glutathione enzymes were determined in the supernatants. RESULTS: Melatonin caused an increase in glutathione level, the activity of glutathione peroxidase as well as glutathione transferase in the examined organs. CONCLUSION: Melatonin may exert some effects on the activity of enzymes engaged in the metabolism of thiol compounds in the cell. Glutathione may be useful for monitoring melatonin's protective role on cell damage.