Analysis of the prevalence of polymorphisms in the glutathione S transferase gene (GST) in cataract patients from Goiânia.

The aim of this study was to determine the prevalence of polymorphisms in the glutathione S-transferase genes GSTM1 and GSTT1 in patients with lens opacity (cataract). Peripheral blood samples were obtained from male and female patients (N = 23) with cataract. The GSTM1 and GSTT1 polymorphic regions were amplified by polymerase chain reaction, and the amplification products were electrophoresed on a 2% agarose gel. The obtained bands were by staining with ethidium bromide. The results were compared by a chi-square test using the BioEstat software (v.5.0). The frequencies of the GSTM1- and GSTT1-null genotypes were higher than those of the GSTM1- and GSTT1-present genotypes. The frequency of GSTT1-null genotypes was approximately 1.7 times higher than that of GSTM1, which was a statistically significant difference (P = 0.0019). Although a consensus remains to be reached on the correlation between genetic polymorphisms in GSTs and cataract susceptibility, the observations from most scientific studies are similar to those reported in this study. Thus, we conclude that the absence of these genes, particularly GSTT1, is correlated with the development of lens opacity.

GSTM1 gene polymorphism and the risk of colorectal cancer in a Saudi Arabian population.

The enzyme glutathione S-transferase Mu 1 (GSTM1) is encoded by the GSTM1 gene. Polymorphisms in GSTM1 affect the detoxifying function of the enzyme variants. This forms the basis of the debate about the impact of the GSTM1 null/present genotype on colorectal carcinoma risk. We tested the potential influence of GSTM1 polymorphisms on the development of colorectal cancer. DNA extracted from 83 samples taken from patients that were previously diagnosed as having colorectal carcinoma and from 35 control subjects who did not have colorectal carcinoma were amplified. GSTM1 genotypes were determined by DNA sequencing. The current study revealed that the majority (69/83, 83%) of colorectal cancer cases harbored the null genotype (GSTM1*0/*0), and the remaining 14 (17%) cases harbored either the GSTM1wt/wt or the GSTM1wt/*0 genotype. In contrast, among the control cases, 23 (65%) had the null genotype (GSTM1*0/*0) and 12 (35%) had either the GSTM1wt/wt or the GSTM1wt/*0 genotype. The current report emphasizes the impact of the GSTM1 null genotype on the increased risk of colorectal carcinoma in Saudi Arabia.

Glutathione S-transferase polymorphisms in varicocele patients: a meta-analysis.

The glutathione S-transferase (GST) family represents a major group of detoxification and antioxidant enzymes. Studies have shown that high oxidative stress levels are associated with varicocele. The objective of this study was to assess the relationship between GSTM1 and GSTT1 null polymorphisms and varicocele using a study group of 497 varicocele patients and 476 control subjects. A systematic literature search (for articles published up to September 2014) utilizing Google Scholar and PubMed was conducted. The chi-square-based Q test and I(2) index were used to evaluate data from retrieved studies. The possible publication bias was evaluated by Begg funnel plot and the Egger test. No statistically significant association was found between GSTM1 or GSTT1 null genotypes and varicocele in the overall data analysis. In a subgroup analysis, only the null GSTM1 genotype was observed at a significantly higher frequency in Caucasian varicocele patients. In the Chinese subgroup, no association was established between the GSTM1 and GSTT1 null genotypes and this condition. More attention should be drawn to oxidative stress-related pathological manifestations for Caucasian varicocele patients.

Is the GSTM1 null polymorphism a risk factor in primary open angle glaucoma?

PURPOSE: To investigate the association of glutathione S-transferase (GST) GSTM1, GSTT1, and GSTP1 genes with the risk of primary open angle glaucoma (POAG) and clinical features of the disease. METHODS: We conducted a case-control study that included 87 Brazilian patients with POAG and 85 healthy controls matched for age, ethnicity, and sex, whose blood samples were genotyped for polymorphisms in GST genes using polymerase chain reaction (PCR) based methods. RESULTS: The GSTM1 null polymorphism was significantly more common in the POAG than in the controls group (OR: 2.1, 95% CI: 1.13-3.9; p=0.018). The combined GSTM1 null/GSTT1+ genotype and GSTM1 null/GSTP1 Ile/Val or Val/Val was more prevalent in POAG patients, being a risk factor for POAG (OR: 2.4, 95% CI: 1.16-4.9; p=0.016 and OR: 2.7, 95% CI: 1.07-6.74; p=0.033, respectively). The GSTM1 null/GSTT1+ genotype were associated with higher levels of IOP of both eyes and with more severe defect of the right eye optic nerve. The GSTM1 null/GSTP1 Ile/Val or Val/Val genotypes were associated with higher levels of IOP and more advanced defect of the right eye optic nerve and visual field. CONCLUSIONS: We demonstrate that GSTM1 null polymorphism is associated with POAG in the Brazilian population.

Menadione stress in Saccharomyces cerevisiae strains deficient in the glutathione transferases.

Using S. cerevisiae as a eukaryotic cell model we have analyzed the involvement of both glutathione transferase isoforms, Gtt1 and Gtt2, in constitutive resistance and adaptive response to menadione, a quinone which can exert its toxicity as redox cycling and/or electrophiles. The detoxification properties, of these enzymes, have also been analyzed by the appearance of S-conjugates in the media. Direct exposure to menadione (20 mM/60 min) showed to be lethal for cells deficient on both Gtt1 and Gtt2 isoforms. However, after pre-treatment with a low menadione concentration, cells deficient in Gtt2 displayed reduced ability to acquire tolerance when compared with the control and the Gtt1 deficient strains. Analyzing the toxic effects of menadione we observed that the gtt2 mutant showed no reduction in lipid peroxidation levels. Moreover, measuring the levels of intracellular oxidation during menadione stress we have shown that the increase of this oxidative stress parameter was due to the capacity menadione possesses in generating reactive oxygen species (ROS) and that both GSH and Gtt2 isoform were required to enhance ROS production. Furthermore, the efflux of the menadione-GSH conjugate, which is related with detoxification of xenobiotic pathways, was not detected in the gtt2 mutant. Taken together, these results suggest that acquisition of tolerance against stress generated by menadione and the process of detoxification through S-conjugates are dependent upon Gtt2 activity. This assessment was corroborated by the increase of GTT2 expression, and not of GTT1, after menadione treatment.