There is still a strong need for new treatment strategies that will maintain remission and prolong survival in patients with acute lymphoblastic leukemia (ALL). The glutathione-S-transferase (GST) enzymes, which are coded by highly polymorphic genes, have been associated with the risk of developing cancer and were found to regulate effect of cancer treatment drugs.
OBJECTIVES: The present study determines the association of GSTM1, GSTP1 and GSTT1 polymorphisms and treatment response in terms of occurrence of adverse events and relapse in ALL in Filipino children.
METHODS: This is a follow up study on the 2007 investigation done by Alcausin et al. which determined the association of the GST P1, M1, and T1 polymorphisms and occurrence of ALL. Four-year follow-up data were available for 46 out of the 50 patients from January 2007 to May 2011. Odds ratios (OR) as measures of association of GST M1, P1 and T1 gene polymorphisms with treatment outcomes were estimated at 95% confidence interval.
RESULTS: Results show a trend towards predisposition to elevation of liver enzymes in patients with GSTT1 and GSTP1 mutant genotypes showing an OR (95% Cl) of 2.0 (0.62-6.49). The presence of GSTM1 null genotype showed a trend towards protection from occurrence of relapse basing on both crude and adjusted ORs, 0.58 (0.16-2.07) and 0.23 (0.05-1.20), respectively. However, these results are not statistically significant.
CONCLUSION: The GSTP1 heterozygous genotype conferred increased predisposition to elevation of liver enzymes while the GSTT1 null genotype was shown to be a possible risk factor towards the occurrence of both infection and elevation of liver enzymes during chemotherapy. Furthermore, the GSTM1 null genotype appears to be protective from occurrence of relapse. It is recommended to do similar large-scale studies in the future to obtain more conclusive results.

Human ; Male ; Female ; Child ; Child Preschool ; Child ; Confidence Intervals ; Follow-up Studies ; Genotype ; Glutathione ; Glutathione S-transferase Pi ; Glutathione Transferase ; Liver ; Precursor Cell Lymphoblastic Leukemia-lymphoma ; Recurrence ; Treatment Outcome ; Glutathione S-transferase M1 ; Glutathione S-transferase T1

AIMTo investigate the relationship between glutathione S-transferases gene polymorphism and susceptibility response to hypoxia.

METHODSIn the case-control study, the gene polymorphisms of glutathione S-transferases were tested in Tibetan mountaineers and sea-level Han Chinese by multiple-PCR and PCR-RELP.

RESULTSThe frequency of GSTT1 null genotype was significant different between Tibetan mountaineers and sea-level Han Chinese (P < 0.05), OR = 1.86 (95% CI = 1.01-3.39), and also for GSTP(1-105) mutant genotype in two groups (P < 0.01), OR = 2.19 (95% CI = 1.16-4.13). There was significant difference between A allele and G allele of GSTP(1-105) groups (P < 0.01). There was no difference for GSTM1 null genotype between two groups (P > 0.05), OR = 0.78 (95% CI = 0.43 - 1.42).

CONCLUSIONGSTT1 and GSTP(1-105) genotype may be associated with susceptibility response to altitude hypoxia.

Adult ; Alleles ; China ; Genotype ; Glutathione S-Transferase pi ; genetics ; Glutathione Transferase ; genetics ; Humans ; Hypoxia ; genetics ; Male ; Mountaineering ; Polymorphism, Genetic ; Reactive Oxygen Species ; metabolism ; Young Adult

OBJECTIVETo assess the association between glutathione-S-transferase gene polymorphisms GSTT1, GSTM1 and GSTP1 and onset of azoospermia.

METHODSMulti-PCR was used to detect GSTM1 and GSTT1 gene deletions. Polymorphisms of GSTP1 were determined with restriction fragment length polymorphism (RFLP) method in 236 azoospermia patients and 142 healthy fertile male controls.

RESULTSThe frequency of M1 (-/-) and P1 (Ile/Val or Val/Val) genotype was 24.65% in the control group, which was significantly higher than that of the patient group (15.68%, P=0.031). Frequency of M1 (-/-), T1 (+/+) and P1 (Ile/Val or Val/Val) genotype was 12.68% in the control group, which was significantly higher than that of the patient group (5.51%, P=0.014).

CONCLUSIONThe M1(-/-) and P1(Ile/Val or Val/Val) genotype and the M1(-/-), T1(+/+) and P1 (Ile/Val or Val/Val) genotype are associated with reduced risk of azoospermia in ethnic Chinese Han population.

Adult ; Asian Continental Ancestry Group ; Azoospermia ; genetics ; Case-Control Studies ; China ; Genotype ; Glutathione S-Transferase pi ; genetics ; Glutathione Transferase ; genetics ; Humans ; Male ; Phenotype ; Polymorphism, Genetic

BACKGROUNDCigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% - 20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population.

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113-->His), exon 4 (His139-->Arg) and GSTP1 polymorphism in exon 5 (Ile105-->Val) in 100 COPD patients and 100 age- and sex-matched healthy controls.

RESULTSThe proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7.09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers (current smokers and ex-smokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls.

CONCLUSIONSmEH exon 3 heterozygotes might be associated with susceptibility to COPD in China. The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.

Aged ; Epoxide Hydrolases ; genetics ; Female ; Genotype ; Glutathione S-Transferase pi ; Glutathione Transferase ; genetics ; Humans ; Isoenzymes ; genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Genetic ; Pulmonary Disease, Chronic Obstructive ; etiology ; genetics

OBJECTIVETo investigate the relationship between genetic polymorphisms of glutathione S-transferase P1 (GSTP1), glutathione S-transferase M1 (GSTM1), and glutathione S-transferase T1 (GSTT1) and urinary level of mercapturic acids of styrene (PHEMAs) in workers exposed to styrene.

METHODSOne hundred and twenty-six workers exposed to styrene were selected as exposure group, and 150 workers without styrene exposure as the control group; all the workers came from a locomotive shell production factory in Shandong Province, China. The PCR-RFLP technique was applied to analyze the individual genetic polymorphisms of GSTP1; the multiplex PCR technique was used to investigate the genetic polymorphisms of GSTM1 and GSTT1; the relationship between genetic polymorphisms of GSTP1, GSTM1, and GSTT1 and urinary level of PHEMAs in workers exposed to styrene was statistically analyzed.

RESULTSThe three genotypes investigated in the study had a distribution in accordance with the Chinese population. With exposure to high- concentration styrene, the individuals carrying GSTP1 (exon5, A105G) AA genotype (wildtype) had a significantly higher urinary level of PHEMAs (43.58 mg/g) than those with mutant genotypes AG (29.769 mg/g) and GG (30.245 mg/g); the urinary level of PHEMAs in individuals carrying wild-type GSTM1 genotype was significantly higher than that in individuals carrying deficient-type GSTM1 genotype (40.197 mg/g vs 28.866 mg/g, P < 0.05); no significant difference in urinary level of PHEMAs was found between individuals carrying wild-type GSTT1 genotype and deficient-type GSTT1 genotype. There was no significant relationship between the three gene polymorphisms and urinary level of PHEMAs in the control group.

CONCLUSIONThe genetic polymorphisms of GSTP1 and GSTM1 may be related to urinary level of PHEMAs in workers exposed to styrene.

Acetylcysteine ; urine ; Adult ; Female ; Genotype ; Glutathione S-Transferase pi ; genetics ; Glutathione Transferase ; genetics ; Humans ; Male ; Occupational Exposure ; Polymorphism, Genetic ; Styrene ; urine ; Young Adult

OBJECTIVETo construct the vectors of human glutathione S-transferase A1 (GSTA1), P1 (GSTP1), T1(GSTT1) genes and express in Escherichia coli (E. coli).

METHODSHuman GSTA1, GSTP1 and GSTT1 gene whole length cDNAs were amplified by RT-PCR and then subcloned into pET-28a(+) vectors. The proteins were expressed in E. coli BL21(DE3). After purified by Ni2+ affinity chromatography, the enzymatic activities of GSTs were measured with 1-chloro-2,4 -dinitrobenzene (CDNB) as substrate.

RESULTSThe correct GSTA1, GSTP1 and GSTT1 genes were cloned. And soluble GSTA1, GSTT1, GSTP1 proteins were expressed in E.coli. After purification, GSTA1, GSTT1 and GSTP1 showed good enzymatic activities, which were 17.55, 0.02, 18.75 μmol·min-1·mg-1, respectively.

CONCLUSIONThe expression plasmids for GSTA1, GSTT1 and GSTP1 have been constructed and the recombinant proteins are expressed successfully.

DNA, Complementary ; genetics ; Escherichia coli ; genetics ; Genetic Vectors ; Glutathione S-Transferase pi ; biosynthesis ; genetics ; Glutathione Transferase ; biosynthesis ; genetics ; Humans ; Recombinant Proteins ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the effect of trans-acting factor(s) on rat glutathione S-transferase P1 gene (rGSTP1) transcription regulation in tumor cells.

METHODSThe binding of trans-acting factor(s) to two enhancers of the rGSTP1 gene, glutathione S-transferase P enhancer I (GPEI) and glutathione S-transferase P enhancer II-1 (GPE II-1), was identified by an electrophoretic mobility shift assay (EMSA). The molecular weight of trans-acting factor was measured in a UV cross-linking experiment.

RESULTSTrans-acting factor interacting with the core sequence of GPEI (cGPEI) were found in human cervical adenocarcinoma cell line (HeLa) and rat hepatoma cell line (CBRH7919). These proteins were not expressed in normal rat liver. Although specific binding proteins that bound to GPE II-1 were detected in all three cell types, a 64 kDa binding protein that exists in HeLa and CBRH7919 cells was absent in normal rat liver.

CONCLUSIONcGPEI, GPEII specific binding proteins expressed in HeLa and CBRH7919 cells may play an important role in the high transcriptional level of the rGSTP1 gene in tumor cells.

Animals ; Carrier Proteins ; metabolism ; Enhancer Elements, Genetic ; physiology ; Gene Expression Regulation, Enzymologic ; Glutathione S-Transferase pi ; Glutathione Transferase ; genetics ; Isoenzymes ; genetics ; Nuclear Proteins ; metabolism ; Rats ; Transcription, Genetic

OBJECTIVETo investigate the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene (1-OHP) excretions in workers under different exposure levels.

METHODSFour hundred and forty-seven occupationally exposed workers from two coking plants and 220 control workers from a wire rod plant were genotyped to analyze the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-OHP excretions.

RESULTSThe urinary 1-OHP concentration in exposed group was much higher than that in control group (4.61 vs 0.34 µmol/mol Cr, P < 0.05). Occupational exposure levels and cigarette smoking were of the dominating factors affecting 1-OHP excretions in urine. After controlling potential confounders, decreased excretion of urinary 1-OHP was associated with GSTP1 I105V AG + GG genotype in coke oven workers (single-gene model, P = 0.012; multi-gene model, P = 0.011) and with GSTT1 null type in the analysis including all subjects (P = 0.055 in both single-gene and multi-gene models). GSTT1 and GSTP1 were interacted on the urinary concentrations of 1-OHP.

CONCLUSIONUrinary 1-OHP concentrations can be modified by GSTM1, GSTT1 and GSTP1 gene polymorphisms, indicating that these genes are involved in the metabolism of polycyclic aromatic hydrocarbons.

Adolescent ; Adult ; Control Groups ; Genotype ; Glutathione S-Transferase pi ; genetics ; Glutathione Transferase ; genetics ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Polymorphism, Single Nucleotide ; Pyrenes ; analysis ; Urinalysis ; Young Adult

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.
Humans ; Male ; Fluorides/adverse effects* ; Semen ; Polymorphism, Genetic ; Glutathione Transferase/genetics* ; Glutathione S-Transferase pi/genetics* ; Infertility, Male/genetics* ; Genotype ; Biomarkers ; Genetic Predisposition to Disease ; Case-Control Studies

OBJECTIVE: To assess the association of polymorphisms of glutathione S-transferase P1 (GSTP1) and phospholipase C epsilon-1 (PLCE1) genes with the susceptibility of primary esophageal cancer and their interaction with environmental factors. METHODS: 162 patients with primary esophageal cancer and 162 healthy controls were recruited in this cross-sectional study. Basic information such as gender, age, history of smoking and alcohol consumption and family history of esophageal cancer were collected. Single nucleotide polymorphisms at A105G locus of GSTP1 gene and rs3765524, rs2274223 and rs3781264 loci of PLCE1 gene were detected. A logistic regression model was established to analyze the risk factors of esophageal cancer and the interaction among the factors. RESULTS: The proportions of individuals with smoking history, family history of esophageal cancer and hot diet in esophageal cancer group were higher than those in the control group (P<0.05). Conditional Logistic regression analysis showed that smoking, family history of esophageal cancer and GG genotype at the rs2274223 locus of PLCE1 gene were the risk factors for esophageal cancer (P<0.05), and AG/GG genotypes at the A105G locus of GSTP1 gene were the protective factors for esophageal cancer (P<0.05). In the two-factor interaction model, both AA genotype at A105G locus of GSTP1 gene and GG genotype at rs2274223 locus of PLCE1 gene had an interaction with smoking, and the risk of esophageal cancer has increased by 83.6% and 85.7%, respectively (P<0.05). AA genotype at A105G locus of GSTP1 gene, GG genotype at rs2274223 locus of PLCE1 gene and smoking constituted the best three-factor interaction model, and the risk of esophageal cancer has increased by 244.0% (P<0.05). Four-factor interaction model analysis showed that the risk of esophageal cancer among individuals with AA genotype at A105G locus of GSTP1 gene, GG genotype at rs2274223 locus of PLCE1 gene, smoking and family history of esophageal cancer has increased by 264.4% (P<0.05). CONCLUSION The AG and GG genotypes at the A105G locus of GSTP1 gene are protective factors for esophageal cancer, and the GG genotype at rs2274223 locus of PLCE1 gene is a risk factor, both of them may interact with smoking and affect the susceptibility to esophageal cancer.
Humans ; Genetic Predisposition to Disease ; Glutathione Transferase/genetics* ; Cross-Sectional Studies ; Case-Control Studies ; Esophageal Neoplasms/genetics* ; Polymorphism, Single Nucleotide ; Genotype ; Risk Factors ; Glutathione S-Transferase pi/genetics*