Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genes coding for the glutathione S-transferase M1 (GSTM1) and Theta 1 (GSTT1) proteins are polymorphic in humans and these genes are absent, or homozygous null, in 10-60% of different ethnic populations. These enzymes catalyze the conjugation of glutathione to numerous carcinogenic chemicals and previous epidemiologic studies have associated the null genotypes of these GST genes with higher risk of cancer. In this study the frequency of GSTM1 and GSTT1 null genotypes was determined in Japanese patients with gastric adenocarcinoma and colorectal adenocarcinoma and compared to frequencies determined in a community-based control group. The frequency of the null GSTM1 genotype in patients with gastric adenocarcinoma (56.8%) showed a statistically significant increase compared to the control group frequency (43.6%) (odds ratio (OR) = 1.70; 95% CI, 1.05-2.76). The frequency of GSTM1 null individuals was also higher among all colorectal adenocarcinoma cases, but this increase did not reach statistical significance. After grouping by tumor site, the GSTM1 null genotype was a risk factor among the subgroup with distal colorectal tumors (61.1%) (OR = 2.03; 95% CI, 1.06-3.90). No consistent difference was observed between smoking patients and corresponding controls for the frequency of the GSTM1 null genotype for either cancer, although a large risk (OR = 5.76; 95% CI 1.18-28.3) was associated with the GSTM1 null genotype in the low smoking group of gastric adenocarcinoma patients. On the other hand, no statistically significant differences were observed in the frequency of null GSTT1 genotypes in gastric (47.5%) or colorectal (48.5%) adenocarcinoma patients when compared with the control population (44.4%). These results suggest that the GSTM1 null genotype may be associated with susceptibility to gastric adenocarcinoma and distal colorectal adenocarcinoma in Japanese; however, the associations observed were relatively weak and additional studies will be needed to confirm these findings.
...
PMID:Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. 882 6

We describe studies to assess the influence of polymorphism in the human glutathione S-transferase GSTM3 gene on susceptibility to high grade astrocytoma. Immunohistochemical studies using a GSTM3-specific antiserum identified expression of the GSTM3 subunit in astrocytes. The relative levels of expression of GSTM1 and GSTM3 in brain cytosols were determined after resolution of these enzymes using chromatofocusing. We found no differences in the level of GSTM3 activity in individuals with GSTM1 null and those with GSTM1-positive genotypes (GSTM1 A, GSTM1 B and GSTM1 A/B). A case-control study was performed to determine if GSTM3 alone or in combination with GSTM1 or GSTT1 influenced susceptibility to high grade astrocytoma. After correction for differences in age and gender, GSTM3 AA was not significantly different in cases compared with controls. No significant interactions between GSTM3 AA and GSTM1 null were identified. The significant interaction between GSTM3 AA and GSTT1 null appeared to result from the strength of the main effect (GSTT1 null). The data show that while GSTM3 is expressed in astrocytes and contributes significantly to total GST activity in human brain, it does not appear to influence susceptibility to high grade astrocytoma. Further, unlike lung, there appears to be no relationship between the level of GSTM3 activity in brain and GSTM1 genotype.
...
PMID:Allelism at the glutathione S-transferase GSTM3 locus: interactions with GSTM1 and GSTT1 as risk factors for astrocytoma. 882 14

Only limited information is available so far concerning the human glutathione S-transferase isoenzyme class theta encoded by the GSTT1 gene. The aim of the study was to characterize individuals in respect to a polymorphic deletion of the GSTT1 gene and to validate these results with the phenotypical determination of the "conjugator status" according to Hallier et al. (1993). Determination of the GSTT1 genotype was done in 40 healthy adults by using an assay based on internal standard controlled polymerase chain reaction. The GSTT1-1 phenotype was determined by measuring the erythrocyte conjugating activity towards methyl chloride using a gas chromatographic assay. Genotypically, 34 individuals out of 40 were classified as GSTT1 positive; the remainder were negative. These results could be confirmed by phenotyping in all but one case. In the present study the frequency of "nonconjugators" was 15%. Our study demonstrates the reliability of the suggested PCR assay for GSTT1 genotyping which is easier to perform than the phenotyping assay and is not affected by confounding factors.
...
PMID:Comparative genotyping and phenotyping of glutathione S-transferase GSTT1. 885 2

A deletion polymorphism in glutathione S-transferase theta (GSTT1) gene was recently discovered in humans. Similar to the GSTM1 gene, GSTT1 is also recognized as a risk modifier in exposed populations. To evaluate the role of genetic polymorphism in health effects, the combined genetic polymorphism of different genes should be taken into consideration. In the present study, we have developed a multiplex PCR approach for simultaneous replication of both genes for molecular analysis. The multiplex PCR protocol was validated using donor DNA with different polymorphic combinations for both genes from two different ethnic populations (North Americans and Egyptians). The prevalence of the GSTM1 null genotype was 51% among North Americans and 44% among Egyptians. The prevalence of the GSTT1 null genotype was 15% among North Americans and 14.7% among Egyptians. Combined polymorphism analysis of both genes revealed that 6.3% of North Americans harbor the deleted genotype of both genes compared to 8.8% of the Egyptians. The data indicate that there is no major difference in allelic distribution of both genes between the ethnic populations. The multiplex PCR assay used in this study has the advantage of reducing the time, effort and cost required to carry out such analysis. It will also significantly enhance the ability to use genetic screening techniques as a potential tool for early detection of health outcomes in exposed populations.
...
PMID:A multiplex PCR procedure for polymorphic analysis of GSTM1 and GSTT1 genes in population studies. 894 18

The importance of polymorphism in the glutathione S-transferase GSTM1, GSTT1 and, cytochrome P450, CYP2D6 loci in the pathogenesis of epithelial ovarian cancer has been assessed in two studies; firstly, a case-control study designed to determine the influence of these genes on susceptibility to this cancer, and secondly, the putative role of these genes in the protection of host cell DNA has been studied by comparing p53 expression in patients with different GSTM1, GSTT1 and CYP2D6 genotypes. The frequencies of GSTM1, GSTT1 and CYP2D6 genotypes in 84 cases and 325 controls were not different. Immunohistochemistry was used to detect p53 expression in 63 of these tumours. Expression was found in 23 tumours. Of the patients demonstrating immunopositivity, 20 (87%) were GSTM1 null. The frequency distributions of GSTM1 genotypes in p53-positive and -negative samples were significantly different (P = 0.002) and those for GSTT1 genotypes approached significance (exact P = 0.057). The proportion of patients with both GSTM1 null and GSTT1 null was also significantly greater in the immunopositive (4/22) than in the immunonegative group (1/40) (P = 0.0493). Single-strand conformational polymorphism (SSCP) analysis was used to detect mutations in the 23 tumour samples demonstrating p53 positivity. A shift in electrophoretic mobility of amplified fragments was found in 11 patients (exons 5, 6, 7 and 8) and these exons were sequenced. In eight samples a mutation was found. No SCCP variants were identified in the other 12 immunopositive patients. Sequencing of exons 4-9 of p53 from these tumours resulted in the detection of mutations in two patients (exons 5 and 7). Thus, in 23 patients who demonstrated immunopositivity, p53 mutations were found in nine patients with GSTM1 null (90.0%). In the 13 patients in whom no mutations were identified, 11 were GSTM1 null (84.6%). The data show that overexpression of p53 is associated with the GSTM1 null genotype. We propose the data are compatible with the view that GSTM1 and GSTT1 are critical in the detoxification of the products of oxidative stress produced during the repair of the ovarian epithelium. Thus, failure to detoxify products of this stress may result in damage to various genes in the host cell, including to p53, resulting in persistent expression of mutant protein. In other patients, oxidative stress effects damage to various genes, but not including p53, resulting in overexpression of wild-type p53.
...
PMID:Epithelial ovarian cancer: influence of polymorphism at the glutathione S-transferase GSTM1 and GSTT1 loci on p53 expression. 895 89

The induction of sister chromatid exchanges (SCEs) by a 48-h treatment with 3,4-epoxybutane-1,2-diol (EBD), a metabolite of 1,3-butadiene, was studied in whole-blood lymphocyte cultures of 22 human donors with known genotypes of two polymorphic glutathione S-transferases (GSTs), GSTT1 and GSTM1. For both genes, donors representing a homozygous 'null' genotype lacking the respective GST gene and isozyme and a 'positive' genotype with at least one intact gene and GST activity were included. The mean frequencies of SCE/cell were similar in all genotype groups: GSTT1 null (n = 10) (mean 22.0 for 250 microM and 32.9 for 500 [corrected] microM of EBD), GSTT1 positive (n = 14) (21.3 and 34.6, respectively), GSTM1 null (n = 10) (20.3 and 33.5) and GSTM1 positive donors (n = 15) (20.6 and 34.8). At 500 microM concentration of EBD, the lymphocyte cultures of all donors showed a significantly decreased replication index. No differences in EDB-induced SCEs or in replication index could be associated with the GSTM1 and GSTT1 genotypes either separately or in combination. When SCE induction by EBD was compared to that of two other known epoxide metabolites of butadiene, 1,2:3,4-diepoxybutane (DEB) was effective at concentrations over two orders of magnitude lower than EBD or 1,2-epoxy-3-butene (MEB). It is concluded that EBD is an efficient inducer of SEC in cultured human lymphocytes, although not quite as effective as MEB and clearly less effective than DEB. Contrary to previous findings with DEB and MEB, the polymorphic GSTM1 and GSTT1 do not appear to be involved in the detoxification of EBD in human lymphocytes.
...
PMID:Induction of sister chromatid exchange by 3,4-expoxybutane-1,2-diol in cultured human lymphocytes of different GSTT1 and GSTM1 genotypes. 898 Jun 97

The glutathione S-transferases (GSTs) catalyze the conjugation of a wide variety of reactive, electrophilic substrates with glutathione, facilitating their excretion. There is also evidence that GSTs can catalyze glutathione conjugation of lipid radicals as well as act in the generation of leukotriene inflammatory mediators. Studying construction carpenters screened for the presence of asbestos-related diseases, we have previously reported that the constitutional deletion of GSTM1 (the gene coding for glutathione S-transferase class mu) is associated with an increased risk of asbestos-related interstitial lung disease, measured radiographically. In the current work, we have further studied this group of workers, investigating the distribution of a novel deletion polymorphism in the newly described GSTT1 gene, that codes for the GST class theta enzyme. A total of 666 carpenters were studied, and 124 (19%) had the deleted genotype. There was no association between the GSTT1 deletion and the radiographic diagnosis of either asbestos-related pleural or parenchymal disease. The GSTM1 deletion remained associated with the presence of x-ray evidence of asbestosis after adjustment for GSTT1 genotype. The GSTM1 null genotype was also associated with a family history of any malignancy. These data suggest that the association of polymorphic GSTs with asbestos-induced radiographic changes is specific for substrates of the GST class mu.
...
PMID:The glutathione S-transferase theta and mu deletion polymorphisms in asbestosis. 905 49

The recently discovered human class theta glutathione S-transferase T1-1 (GSTT1-1) is responsible for the GSH-dependent detoxification of naturally occurring monohalomethanes. The detoxifying role of GSTT1-1 has not been investigated in cancer susceptibility and the polymorphism of the protein is unknown in different populations. The purpose of our work was to produce a panel of mouse monoclonal antibodies (MAbs) that could bind to different regions of the GSTT1-1 protein and would help us select suitable MAbs for Western blot analyses and immunohistochemistry, and develop an ELISA assay for detection of GSTT1-1 in whole blood. Six highly specific MAbs were generated against GSTT1-1. Out of six MAbs, one was able to recognize only the native form of the enzyme and possesses two binding sites on the dimeric GSTT1-1 molecule. The other five MAbs bind to both native and denatured GSTT1-1 enzyme in direct and antigen capture ELISA or Western blot. The antibodies recognize at least four different epitopes on the GSTT1-1 molecule. Using MAbs 4G1 and 2D8, a sensitive ELISA assay for determination of GSTT1-1 in whole blood was developed.
...
PMID:Production and characterization of monoclonal antibodies against class theta glutathione S-transferase T1-1. 906 89

While cigarette smoking and alcohol consumption have been linked to laryngeal squamous cell carcinoma (SCC), the role of genetic factors in determining individual susceptibility is unknown. We describe the role of allelism at the glutathione S-transferase GSTM1, GSTM3, GSTT1 and cytochrome P450 CYP1A1, CYP2E1, CYP2D6 loci in determining individual susceptibility to laryngeal SCC. Enzyme genotypes were determined using polymerase chain reaction and restriction enzyme digestion of leukocyte DNA collected from 269 patients with T1-T4 laryngeal carcinomas and 216 controls. While the frequencies of the heterozygote GSTM1 A/B genotype and the homozygote GSTM3 B/B genotype were statistically significantly lower in the patients with tumors than in controls, the frequency of the GSTT1 null genotype was higher in the patients than in controls. The data suggest that allelism at GST loci mediates susceptibility to SCC of the larynx. GSTM1 A/B and GSTM3 B/B appear to be associated with reduced risk, while GSTT1 null may confer increased risk. These findings are compatible with the view that genetic predisposition is important in determining risk for this cancer.
...
PMID:Glutathione S-transferase and cytochrome P450 genotypes as risk factors for laryngeal carcinoma. 906 51

Basal cell carcinoma (BCC) places increasing burdens on clinicians; incidence is rising and patients may develop multiple primary tumors. Although UV exposure is critical, many patients develop tumors at less-exposed sites, such as the trunk, suggesting a genetic predisposition. We previously showed that polymorphism in loci encoding the detoxifying enzymes, glutathione S-transferase (GSTM1, GSTM3, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) influences susceptibility to BCC. We now describe a case-control approach in 345 patients with BCC that examines the role of these polymorphisms and patient characteristics (age, gender, skin type, hair color, eye color, smoking, occupation) in determining susceptibility to truncal tumors. GST and CYP genotypes were identified using polymerase chain reaction-based methods. Patients with one or more truncal tumors were significantly younger (p = 0.0170) than those with no truncal tumors. Male gender also appeared more common in the truncal tumor group, although this did not achieve significance (p = 0.0925). Patients whose first tumor was truncal had significantly more tumors (p = 0.0297). GSTT1 null (p = 0.0245, odds ratio 2.24) and CYP1A1 Ile/Ile (p = 0.0386, odds ratio 2.86) were associated with truncal site after correction for age and gender. The combination, GSTT1 null and CYP1A1 Ile/Ile, was particularly significant (p = 0.0059, odds ratio = 2.95). These effects were present after correction for tumor numbers. These data show first, patients with truncal tumors constitute a high-risk group for BCC, second, a significant genetic influence on BCC site, and third, a significant interaction between GSTT1 and CYP1A1 genotypes.
...
PMID:Truncal tumor site is associated with high risk of multiple basal cell carcinoma and is influenced by glutathione S-transferase, GSTT1, and cytochrome P450, CYP1A1 genotypes, and their interaction. 907 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---