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

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

The function of the glutathione-related detoxification system plays an important role to ensure an uncomplicated pregnancy outcome. This study was performed to investigate whether the components of the glutathione-related detoxification system are equally distributed among the different cotelydons in the human placenta. We measured glutathione, cysteine, glutathione S-transferase (GST) isoenzyme levels (GSTA1+A2, GSTP1, GSTM1 and GSTT1), enzyme activities of glutathione S-transferase and glutathione peroxidases, protein carbonyl levels, and antioxidant capacities at twelve different standardized positions in six placentae from healthy women after uncomplicated pregnancy and vaginal delivery. Data were statistically evaluated with a Friedman two-way ANOVA with Bonferroni correction. 'Foetal'-side values were not significantly different from those at the 'maternal'-side. Except for GSTA1+A2, no significant differences were found between different sampling sites indicating that the distribution of all parameters measured was homogenous throughout the placenta. Since levels of GSTA1+A2 were minor compared to those of GSTP1 and GSTT1, the clinical relevance of this heterogeneity may be limited. These results implicate that the location of sampling is not important as long as biopsies are taken from physiological cotelydons.
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PMID:Distribution of components of the glutathione detoxification system across the human placenta after uncomplicated vaginal deliveries. 1213 47

Oxidative stress is believed to play an important role in the pathogenesis of smoking-induced chronic obstructive pulmonary disease. We hypothesized that polymorphisms of antioxidant genes glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, and heme oxygenase-1 (HMOX1) would be associated with susceptibility to accelerated decline of lung function in smokers. We genotyped 621 subjects (299 rapid decliners [change in forced expiratory volume in 1 second (DeltaFEV(1)) = -152 +/- 2.5 ml/year] and 322 nondecliners [DeltaFEV(1) = +15 +/- 1.5 ml/year]) selected from among smokers followed for 5 years in the National Heart, Lung, and Blood Institute Lung Health Study. Because genotype frequencies were different between ethnic groups, we limited the association study to 594 whites (286 rapid decliners and 308 nondecliners). None of the genotypes studied had a statistically significant effect on decline of lung function when analyzed separately. There was an association between rapid decline of lung function and presence of all three GST polymorphisms (odds ratio [OR] = 2.83; p = 0.03). A combination of a family history of chronic obstructive pulmonary disease with GSTP1 105Ile/Ile genotype was also associated with rapid decline of lung function (OR = 2.20; p = 0.01). However, due to the multiple comparisons that were made, these associations may represent type 1 error. There was no association between HMOX1 (GT)n alleles and the rate of decline in lung function in smokers.
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PMID:Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers. 1215 64

The relationships between glutathione S-transferase (GST) M1, GSTT1, and GSTP1 genotypes and acute respiratory illness were investigated in a cohort of fourth grade school children aged 9-11 years who resided in 12 southern California communities. We used respiratory illness-related absences as a measure of respiratory illness occurrence. We ascertained respiratory illness-related school absences using an active surveillance system from January 1996 through June 1996. Genotypes for GSTM1 (null versus present), GSTT1 (null versus present), and GSTP1 (Ile105Val) were determined using genomic DNA from buccal cell specimens. The effects of GST genotypes on respiratory illness were assessed using stratified absence incidence rates and Poisson regression models. GSTP1 genotype was associated with risk for respiratory illness severe enough to result in a school absence. Children who were homozygous for the Val105 variant allele had lower incidence rates of upper and lower respiratory illnesses than did children who were homozygous for the Val105 allele. Children inheriting at least one Val105 allele were protected from respiratory illnesses (relative risk, 0.80; 95% confidence interval, 0.65-0.99). GSTM1 and T1 genotypes were not associated with respiratory illness. We conclude that GSTP1 genotype influences the risk or severity of respiratory infections in school-aged children.
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PMID:Effects of glutathione S-transferase P1, M1, and T1 on acute respiratory illness in school children. 1215 68

Glutathione S-transferases (GSTs) catalyze the conjugation of glutathione to numerous potentially genotoxic compounds. The GSTM1 gene codes for the enzyme glutathione S-transferase-mu, the GSTT1 gene codes for the enzyme glutathione S-transferase-theta, and the GSTP1 gene codes for the enzyme glutathione S-transferase-pi. GSTM1 is polymorphically expressed, and three alleles have been identified (GSTM1-0, GSTM1a, and GSTM1b). Two functionally different genotypes at the GSTT1 locus have been described. Individuals with homozygous deletions of GSTM or GSTT have reduced or no glutathione S-transferase activity and therefore may be unable to eliminate electrophilic carcinogens as efficiently. However, results of epidemiologic studies do not confirm associations between GSTM1, GSTT1, and GSTP1 and epithelial ovarian cancer.
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PMID:Glutathione S-transferase polymorphisms and risk of ovarian cancer: a HuGE review. 1217 91

Previous studies have suggested that GST genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In this study we investigated GSTM1, GSTT1 and GSTP1 status in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. Cases were all patients (n=94) currently with, or with a history of, tumours of the lung, trachea or bronchus. The control group were all other patients (n=165) who were free of benign and malignant tumours both at the time of, or prior to, diagnosis. All patients were interviewed for information on lifestyle risk factors, and DNA extracted from bronchial lavage and blood samples was used for genotyping. GSTM1 null genotype was associated with decreased lung cancer risk (odds ratio (OR) 0.50, 95% confidence interval (CI) 0.29-0.87), particularly among men (OR 0.43, 95% CI 0.21-0.87) and those above the median age (OR 0.33, 95% CI 0.15-0.70). No difference in GSTT1 and GSTP1 genotype distribution was seen between cases and controls. The GSTM1 null genotype was associated with a decreased risk of squamous cell carcinoma: the OR, adjusted for age, sex and pack years was 0.32 (95% CI 0.12-0.82). As previous studies have reported that the GSTM1 null genotype is associated with an increased lung cancer risk, further work is required to determine whether the observed association is true, or whether it arises from bias or confounding factors.
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PMID:GSTM1, GSTT1 and GSTP1 polymorphisms and lung cancer risk. 1217 48

Polymorphisms in the glutathione S-transferase (GST) genes, a superfamily that plays a key role in carcinogen metabolism, have been associated with an increased susceptibility to several types of cancer. We wished to evaluate whether variant allelic forms of GST isoenzymes were associated with an increased susceptibility for brain tumors and age of tumor onset. Here, we examined 394 brain tumors (221 adult and 173 pediatric cases consisting of 197 astrocytic and 197 non-astrocytic tumors) to determine the frequency of polymorphisms in the GSTM1, GSTT1, and GSTP1 genes compared to a healthy control population. Our data shows that the frequency of GST polymorphisms varies not only between adult and pediatric patients with brain tumors and healthy controls, but also between different histological subtypes of brain tumors occurring in pediatric patients. We found (i) a statistically significant increase in the frequency of the functional GSTM1 allele in high-grade pediatric astrocytomas (p < 0.002), (ii) a significant increase in the frequency of the rare GSTP1 variant Val114/Val114 in pediatric astrocytomas (p < 0.002), and (iii) a significant increase in the frequency of the rare GSTP1 Val114/Val114 genotype among pediatric tumors showing microsatellite instability (MSI) due to defects in mismatch repair (MMR) proteins (p = 0.003). Our results suggest that GSTM1 and GSTP1 polymorphisms may play a role in brain tumor susceptibility by histological subtype, particularly high-grade pediatric astrocytomas. Moreover, the presence of the genetic modifier GSTP1 Val114/Val14 genotype may begin to define a high-risk genotype for cancer susceptibility in the pediatric population.
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PMID:Identification of glutathione S-transferase (GST) polymorphisms in brain tumors and association with susceptibility to pediatric astrocytomas. 1224 Nov 5

Liver disease in patients with cystic fibrosis (CF) is inconstant and has not yet been clearly related to any specific risk factor. While the expression of cystic fibrosis transmembrane conductance regulator (CFTR) is restricted to the biliary epithelium in the liver, recent findings indicate that CFTR modulates reduced glutathione (GSH) transport and that CFTR dysfunction creates an imbalance in the antioxidant defense. Among liver detoxifying enzymes, the glutathione S-transferases (GSTs) play a key role in the protection against oxidative stress. Because oxidative injury contributes to the development of liver disease, we hypothesized that 2 members of the GST superfamily, GSTM1 and GSTP1, which are expressed in the biliary epithelium, could influence the hepatic status in patients with CF. The potential impact of GSTM1 and GSTP1 gene polymorphisms was assessed in 106 children with CF (mean age, 11.5 years). Based on polymerase chain reaction/restriction fragment length polymorphism analysis, we found that the frequency of GSTP1-Ile(105)/Ile(105) genotype was significantly higher in patients with CF with liver disease than in those without (P <.03). Among the youngest patients, aged 6 years, GSTP1-Ile(105)/Ile(105) genotype was associated with a 8-fold increase in the risk of liver disease compared with other GSTP1 genotypes (P =.002). No association between the GSTM1 genotype and liver status was documented. In conclusion, GSTP1-Ile(105)-encoding allele contributes to hepatic dysfunction in CF. Identification of this polymorphism may have prognostic value and prompt early treatment in patients with CF with an increased risk of liver disease.
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PMID:Liver disease in pediatric patients with cystic fibrosis is associated with glutathione S-transferase P1 polymorphism. 1260 71

Two polymorphic sites of the microsomal epoxide hydrolase gene (EPHX1, 113Tyr-->113His, 139His-->139Arg) and four glutathione S-transferase genes (GSTM1, GSTM3, GSTP1, GSTT1) were genotyped in a group of patients with larynx cancer (N=204) and in a group of healthy controls (N=203), all Spanish caucasians. After adjusting for gender, age, and tobacco smoking, none of the polymorphisms alone were found to be associated with larynx cancer risk. The analysis of EPHX1/GST combinations, however, showed a significant over-representation of patients with a combination of 113Tyr/113Tyr EPHX1 and 105Ile/105Ile GSTP1 (adjusted odds ratio (OR): 1.95; 95% confidence interval (CI): 1.02-3.78). The calculation of the predicted epoxide hydrolase (EH) activity also showed an increased risk for the individuals with both predicted high activity EH and 105Ile/105Ile GSTP1 (OR: 2.90; 95% CI: 1.10-7.67). These results on larynx cancer tend to confirm a former study on lung cancer (Cancer Lett. 173 (2001) 155) suggesting the existence of an interaction between variants of EH and GSTpi, both enzymes being involved in the metabolism of aromatic hydrocarbons, that may increase susceptibility to tobacco-related cancers.
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PMID:Microsomal epoxide hydrolase and glutathione S-transferase polymorphisms in relation to laryngeal carcinoma risk. 1235 56

Individual differences in lung cancer susceptibility should be considered for effective lung cancer prevention. We investigated the CYP2E1, ADH3, and GSTP1 genetic polymorphisms that biotransform xenobiotic carcinogens, and variations of their enzyme activity in Caucasian lung tissues (N=28), and found a variant distribution in pulmonary ADH and CYP2E1 activity. The ADH3*1/*1 subjects (N=8) showed significantly higher ADH activity than ADH3*2/*2 (N=3) subjects (P<0.01). On the other hand, we found a 5-fold variation in the pulmonary CYP2E1 activity using a sensitive HLPC/EC based technique. A subject with the CYP2E1-c/t allele showed 2-fold higher CYP2E1 activity than subjects with the c/c allele (N=14). GSTP1 expression comprised 83% of the total pulmonary GSTs. However, neither the GSTP1 polymorphism, nor other lifestyle factors, such as age, gender, smoking status, were found to be associated with pulmonary GST expression. In conclusion, subjects with the ADH3*1 allele showed higher ADH activity and acetaldehyde-DNA adducts in lung than other subjects; thus, the ADH3*1 allele could be considered a risk factor for lung cancer.
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PMID:Effects of the ADH3, CYP2E1, and GSTP1 genetic polymorphisms on their expressions in Caucasian lung tissue. 1236 88

DNA damage from polycyclic aromatic hydrocarbons (PAH) and other aromatic/hydrophobic compounds has been implicated in case-control studies as a risk factor for lung cancer, as have common polymorphisms in the glutathione S-transferase (GST) genes involved in carcinogen detoxification. However, their joint effects have not been evaluated in prospective studies, leaving open questions about predictive value of these biomarkers. In this matched case-control study nested within the prospective Physicians' Health Study, we evaluated whether biomarkers measured in white blood cells (WBC) significantly predicted risk, alone and in combination, after controlling for level of smoking. The biomarkers reported here are aromatic/hydrophobic-DNA adducts and polymorphisms in genes coding for the GSTM1 and GSTP1 enzymes. Our study population was composed of 89 cases of primary lung cancer and 173 controls, matched in a 1:2 ratio on smoking, age and duration of follow up. Adducts were measured in WBC DNA by the nuclease P1-enhanced (32)P-post-labeling method. Genotypes (GSTM1 null versus non-null and GSTP1 Val versus GSTP1 Ile) were determined by genomic amplification and restriction fragment length polymorphism analysis. Among current smokers, adducts were significant predictors of lung cancer risk (after adjusting for GST genotypes, OR = 3.10, 95% CI 1.07, 9.01). The combined GSTM1 null/GSTP1 Val genotype was associated with lung cancer overall and especially among former smokers, before and after adjusting for adducts (OR for former smokers = 4.21, CI 1.08, 16.41; adjusted OR = 4.68, CI 1.17, 18.71). Among cases only, adducts were significantly higher among current or former smokers with the GSTM1 non-null/GSTP1 Ile genotype. The two risk factors (adducts and genotypes) appear to be independent predictors of risk. The findings underscore the complex and important role of biological susceptibility as a determinant of risk from carcinogens found in tobacco smoke and other environmental compounds.
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PMID:Associations between carcinogen-DNA damage, glutathione S-transferase genotypes, and risk of lung cancer in the prospective Physicians' Health Cohort Study. 1237 72


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