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Objective@#To analyze the changes of protein expression in aqueous humor of patients with primary open angle glaucoma (POAG), and to explore the biological markers and potential therapeutic targets associated with disease occurrence.@*Methods@#A retrospective case-control study was adopted.Ten patients with age-related cataract and 10 patients with POAG combined with cataract.were collected at the Tianjin Medical University Eye Hospital from October 2016 to December 2017.In the process of surgery, 100 μl of aqueous humor were collected with 1 ml syringe and No.1 needle through the surgical access.Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry.The differential significance test was performed by Maxquant significances A. The differential proteins of the two groups were screened and determined with the conditions of P<0.05 and difference multiple>2.The biological big data was annotated by the function of GO and KEGG.The study was approved by the Ethics Committee of the Tianjin Medical University Eye Hospital (No.2013KY[L]-10). Patients and their guardians all signed the informed consent.@*Results@#Ninty-seven differential proteins were detected in this proteomic analysis, including 48 up-regulated proteins and 49 down-regulated proteins.GO analysis significantly differs in protein function involved in many aspects, some different proteins including lipopolysaccharide-binding protein (LBP), cluster of Differentiation 163(CD163), C-reactive protein (CRP), annexin A1 (ANXA1) were involved in inflammation; redox-related proteins were glutathione S-transferase P (GSTP1), thioredoxin (TXN), some different proteins related with cell adhesion movement were cartilage oligomeric matrix protein (COMP), desmocollin-2 (DSC2) and laminin subunit beta-2 (LAMB2); procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1), solid protein (tenascin, TNC) are associated with fibrosis; some different proteins related to nerve growth were reelin (RELN), semaphorin-3F(SEMA3F), semaphorin-4B(SEMA4B). Metabolism-related proteins included pyruvate kinase (PKM), carb oxypeptidase N subunit 2 (CPN2) and so on.KEGG analysis indicated that the expression of NrF2/ERK signaling pathway and TGF-β/NF-κB signaling pathway were different between the two groups.@*Conclusions@#The expression of GSTP1 and TXN in the aqueous humor of POAG is significantly decreased, which may regulate cell adhesion and activity and expression of extracellular matrix by regulating NrF2/ERK1/2 and TGF-β/NF-κB signaling pathways.GSTP1 and TXN may serve as a potential biomarker and therapeutic target of POAG.
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Objective To analyze the changes of protein expression in aqueous humor of patients with primary open angle glaucoma ( POAG ) , and to explore the biological markers and potential therapeutic targets associated with disease occurrence. Methods A retrospective case-control study was adopted. Ten patients with age-related cataract and 10 patients with POAG combined with cataract. were collected at the Tianjin Medical University Eye Hospital from October 2016 to December 2017. In the process of surgery,100 μl of aqueous humor were collected with 1 ml syringe and No. 1 needle through the surgical access. Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry. The differential significance test was performed by Maxquant significances A. The differential proteins of the two groups were screened and determined with the conditions of P<0. 05 and difference multiple>2. The biological big data was annotated by the function of GO and KEGG. The study was approved by the Ethics Committee of the Tianjin Medical University Eye Hospital (No. 2013KY[L]-10). Patients and their guardians all signed the informed consent. Results Ninty-seven differential proteins were detected in this proteomic analysis,including 48 up-regulated proteins and 49 down-regulated proteins. GO analysis significantly differs in protein function involved in many aspects,some different proteins including lipopolysaccharide-binding protein (LBP),cluster of Differentiation 163(CD163),C-reactive protein (CRP),annexin A1 (ANXA1) were involved in inflammation;redox-related proteins were glutathione S-transferase P (GSTP1),thioredoxin (TXN), some different proteins related with cell adhesion movement were cartilage oligomeric matrix protein ( COMP ) , desmocollin-2 ( DSC2 ) and laminin subunit beta-2 ( LAMB2 );procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1),solid protein (tenascin,TNC) are associated with fibrosis;some different proteins related to nerve growth were reelin (RELN),semaphorin-3F(SEMA3F),semaphorin-4B(SEMA4B). Metabolism-related proteins included pyruvate kinase ( PKM ) , carb oxypeptidase N subunit 2 ( CPN2 ) and so on. KEGG analysis indicated that the expression of NrF2/ERK signaling pathway and TGF-β/NF-κB signaling pathway were different between the two groups. Conclusions The expression of GSTP1 and TXN in the aqueous humor of POAG is significantly decreased,which may regulate cell adhesion and activity and expression of extracellular matrix by regulating NrF2/ERK1/2 and TGF-β/NF-κB signaling pathways. GSTP1 and TXN may serve as a potential biomarker and therapeutic target of POAG.
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Objective: To study the expressions of AAX14401 in the normal bladder tissue and the human bladder transitional cell carcinoma tissue, and to analyze its function in the occurrence and development of bladder cancer. Methods: Seventy-five cases of specimens of bladder transitional cell carcinoma were collected and used as experimental group and 12 cases of normal bladder mucosa specimens were selected as control group. The positive expression rates of glutathione S-transferase pi-1 (GSTP1) and AAX14401 were detected by immunohistochemistry. The differences of positive expression rates of GSTP1 and AAX14401 proteins between bladder cancer tissue and normal bladder tissue were analyzed. Results: The positive expression rate of GSTP1 protein in normal bladder tissue was 58.3%, while it was 90.7% in bladder cancer tissue, and the difference between them was significant (P<0. 01). The positive expression rate of AAX14401 protein in normal bladder tissue was 0%, while it was 2. 7% in blandder cancer tissue, and there was no significant difference between them (P= 0. 596). There was no one with positive AAX14401 expression and positive GSTP1 expression in bladder cancer tissue at the same time. There were 2 cases with positive AAX14401 expression in bladder cancer tissue with negative GSTP1 expression; there was a negative correlation between the positive expressions of AAX14401 and GSTP1 proteins in bladder cancer (r=-0. 274, P=0. 018). Conclusion: The expression of AAX14401 protein may promote the incidence and progression of bladder cancer.
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Objective: To evaluate the association of glutathione S-Transferase P1 (GSTP 1) gene promoter methylation with the risk of prostate cancer. Methods: A computer-based online search was performed in PubMed, Embase, Cochrane Library, ISI Web of Science and China National Knowledge Infrastructure (CNKI) databases. According to the inclusion and exclusion criteria, the literatures about GSTP 1 gene promoter methylation and the risk of prostate cancer were selected. The difference in the incidence rate of GSTP 1 promoter methylation was compared between the prostate cancer tissues and the non-prostate cancer tissues, as well as in the blood or urine between the prostate cancer patients and the non-prostate cancer patients. The outcome measurements were odds ratio (OR ) with 95% confidence interval (95% CI ) for the association between the GSTP 1 gene promoter methylation and the risk of prostate cancer. The Meta-Analysis was performed using Stata 12.0 software. Results: A total of 19 studies including 1 889 samples were included in this Meta-Analysis. The result of the Meta-Analysis showed that GSTP 1 gene promoter methylation increased the risk of prostate cancer by 23.49 times [OR : 23.49 (95% CI : 13.14-42.01), P < 0.001]. Conclusion: GSTP 1 gene promoter methylation may increase the risk of prostate cancer.
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Objective To investigate the association of genetic polymorphisms of ATIC and GSTP1 with plasma concentrations and adverse reactions of high-dose methotrexate( HD-MTX)in children with acute lymphoblastic leukemia (ALL). Methods A total of 70 peripheral blood samples were obtained from ALL children for extraction of genome DNA.The gene polymorphisms of ATIC T26293C and GSTP1 A313G locus were examined by using PCR and direct sequencing.Enzyme multiplied immunoassay technique(EMIT)was employed to determine the plasma concentration of MTX in 48 h.Clinical data of patients were collected during HD-MTX chemotherapy,and the adverse reactions were statistically analyzed.The associations of ATIC and GSTP1 genotypes with MTX plasma concentration and adverse reactions were investigated. Results There were genetic polymorphisms at the SNP of ATIC T26293C and GSTP1 A313G.At the SNP of ATIC T26293C,the percentages of TT, CT and CC genotypes in ALL children were 4.35%,39.13% and 56.52%,respectively,and the frequencies of T and C alleles were 23.91% and 76.09%.At the SNP of GSTP1 A313G,the percentages of AA,GA and GG genotype were 68.57%,28.57%and 2.86%,respectively,in ALL children. The frequencies of A and G alleles were 82. 86% and 17. 14%,respectively. No statistically significant difference was found in the ratio of blood MTX concentration to MTX dose at 48 h between children with different genotypes(P>0.05).In the GSTP1 A313G site,genotypes that induced the gastrointestinal reactions in the order from low to high were AA,GA,GG,and there was a significant association between gene polymorphism and gastrointestinal side effects(P<0.05).In the GSTP1 A313G site,genotypes that induced myelosuppression in the order of low to high were GG,AA, GA,and a significant association was noted between gene polymorphism and myelosuppression(P<0.05). Conclusion There are significant associations between GSTP1 A313G polymorphism and gastrointestinal side effects or myelosuppression after HD-MTX chemotherapy in ALL children.
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Objective To detect the single nucleotide polymorphisms of rs1695 of glutathione S-transferase P1 [GSTP1 (rs1695)] in the peripheral blood of breast cancer patients, and to analyze its association with the efficacy of paclitaxel/ anthracycline-based chemotherapy in stage IV breast cancer patients. Methods The genotypes of GSTP1 (rs1695) gene polymorphisms were determined by polymerase chain reaction (PCR)-high resolution melting (HRM) method in 128 cases of female stage V breast cancer, and 10% samples were tested by gene sequencing technique according to the PCR-HRM results. The SPSS 11. 5 software was used for statistical analysis, the Hardy-Weinberg equilibrium test was used for genetic equilibrium distribution of genotypes, the correlation of different genotypes with chemotherapy responses was analyzed by the X2 test and Fisher' exact test, and non-conditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence Hardy-Weinberg test suggested that our research had a group representation (P>0. 05). Chemotherapy with paclitaxel/anthracycline yielded an efficiency rate of 57. 03% (73/128) and an inefficiency rate of 42. 97% (55/128), and in the latter the stable disease accounted for 18. 75% (24/ 128). Patients carrying GSTP1 (rs1695)AG/GG genotype hada better response to chemotherapy than those carrying AA genotype (OR = 4. 139, 95% CI; 1. 907-8. 975, P<0. 01), and GSTP1 (rs1695) G gene carriers had a better response than A gene carriers (X2 = 12. 163, P<0. 01). Among the 70 cases receiving combined treatment with anthracycline, those carrying GSTP1 (rs1695)AG/GG genotypehada better response than those carrying AA genotype (OR = 4. 016, 95% CI; 1. 40411. 483, P<0. 01), and GSTP1 (rs1695) G gene carriers had a better response than A gene carriers (X2 = 5. 943, P<0. 05). Conclusion Genetic polymorphisms in GSTP1 (rs1695) can serve as a genetic marker to forecast the chemotherapy response of stage V breast cancer patients to paclitaxel/anthracycline-based chemotherapy, which is worthy of further large sample study.
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Objective To study the relationships of Helicobacter pylori (Hp) infection and genetic polymorphisms of glutathione s-transferase P1 (GSTP1) with gastric cancer (GC). Methods The 98 patients with GC and 149 controls with normal finding at endoscopy were enrolled for this study. The rapid urease test (RUT), 13C- urea breath test (13C-UBT) and Giemsa staining of biopsy samples were used to check Hp infection. PCR-based restriction fragment length polymorphisms (PCR-RFLP) was used to detect GSTP1 genotype. Results The rate of Hp infection was higher in GC group than in control group (54.1% vs. 40.9%, x2 =4.11, P＜0. 05). The risk of GC would significantly increase in the GSTP1 homozygous mutant gene (MM) group with Hp infection (OR=5.44, 95%CI 1. 26-26. 79, x2=7.13, P＜0.05). Conclusions Hp infection and GSTP1 genetic polymorphisms are associated with gastric cancer risk in the elderly.
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PURPOSE: The glutathione-S-transferase (GST)P1, GSTM1, and GSTT1 genotypes have been associated with an increased risk of prostate, bladder, and lung cancers. The aim of this study was to investigate the association between the GSTP1, GSTM1, and GSTT1 genotypes and the risk of prostate cancer in Korean men. MATERIALS AND METHODS: The study group consisted of 166 patients with histologically confirmed prostate cancer. The control group consisted of 327 healthy, cancer-free individuals. The diagnosis of prostate cancer was made by transrectal ultrasound-guided biopsy. Patients with prostatic adenocarcinoma were divided into organ-confined ( or =pT3) subgroups. The histological grades were subdivided according to the Gleason score. The GSTP1, GSTM1, and GSTT1 genotypes were determined by using polymerase chain reaction-based methods. The relationship among GSTP1, GSTM1, and GSTT1 polymorphisms and prostate cancer in a case-control study was investigated. RESULTS: The frequency of the GSTM1 null genotype in the prostate cancer group (54.2%) was higher than in the control group (odds ratio=1.53, 95% confidence interval=1.20-1.96). The comparison of the GSTP1, GSTM1, and GSTT1 genotypes and cancer prognostic factors, such as staging and grading, showed no statistical significance. CONCLUSIONS: An increased risk for prostate cancer may be associated with the GSTM1 null genotype in Korean men, but no association was found with the GSTT1 or GSTP1 genotypes.
Subject(s)
Humans , Male , Adenocarcinoma , Biopsy , Case-Control Studies , Genotype , Glutathione Transferase , Lung Neoplasms , Neoplasm Grading , Prostate , Prostatic Neoplasms , Urinary BladderABSTRACT
Objective To detect thc distribution ofpolymorphism of GSTP1 and infection rate of Helicobacter pylori (H. Pylori) in different kinds of gastric intestinal metaplasia (IM) and to explore the relationship between entergenic factor-polymorphism of GSTP1 and extogenic factor-H, pylori infection, to determine thc risk of subtype of IM. Methods There were 381 cases in total, including 143 CGS( + ) and 238 IM. H. E. Stain was used for pathological diagnosis. HID-AB-pH2.5 methods were used to classify the IM. ELISA method was used to detect the antibody of H. Pylor-IgG.Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to analyze the genotype. Results Frequency of G genotype was higher in the IM group, when compared to the CGS ( + ) groups (P＜0.05). The positive rate of H. Pyloriwas statistically higher than CGS( + )(P＜0.01 ). By effect-modified model analysis, GSTP1 gene polymorphsim and H. Pyloriinfection presented a positive interaction in the stage IM,with the OR value as 9.386 (95%CI:3.736-23.580) after adjusted by age and gender. The synergy index was 2.078 and the attributable proportion of interaction was 46.36%. The positive rate of H. Pyloriwere statistically bighter than CGS ( + ) group in subtype IM Ⅰ , subtype IM Ⅱ and Ⅲ (P＜0.01). The frequency of G genotype was higher in the IM Ⅱ and Ⅲ group, when compared with the IM Ⅰ groups (P＜0.01). By effectmodified model analysis, in the stage of IM Ⅱ and Ⅲ, GSTP1 gene polymorphsim and H. Pylori infection also presented a positive interaction, with OR value as 24.487 (95%CI: 7.731-77.735 )after adjusted by age and gender, with its synergy index as 1.844, and attributable proportion of interaction as 43.89%. Conclusion The infection of H.pyloriand polymorphism GSTP1 gene appeared to be both the external and internal factors, respectively. In the stage of IM, GSTP1 gene polymorphsim and H. Pylori infection also presented a positive interaction, expecially in the IM Ⅱ and Ⅲ.
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BACKGROUND AND OBJECTIVES: Genetic factors play a role in the etiology of allergic rhinitis. The glutathione S-transferase (GSTP1) is one of the detoxifying enzymes for oxidative stress. The purpose of this study is to examine Polymorphisms of whether there is an association between some alleles of GSTP1 genes and allergic rhinitis. SUBJECTS AND METHOD: Patients with allergic rhinitis were selected on the basis of the following criteria: 1) watery rhinorrhea, sneezing, nasal obstruction and/or itching for longer 3months and 2) positive reaction at the allergic skin prick test for DP, DF allergen and 3) positive reaction at specific IgE RAST for DP, DF allergen. GSTP1 gene polymorphisms in exon5 (Ile105Val) were analyzed by polymerase chain reaction (PCR) with restriction fragment length polymorphisms (RFLP) in 149 patients with allergic rhinitis and 156 healthy control subjects. RESULTS: In allergic rhinitis, Ile105/Ile105 were 106 cases (71.1%), Ile105/Val105 were 42 cases (28.2%), Val105/Val105 were 1 case (0.7%) and in normal controls, Ile105/Ile105 were 100 cases (64.1%), Ile105/Val105 were 45 cases (28.8%), Val105/Val105 were 11 cases (7.1%)(p=0.004). CONCLUSION: Genetic polymorphism of Val105/Val105 in GSTP1 may be protective genotypes in allergic rhinitis.
Subject(s)
Humans , Alleles , Genotype , Glutathione Transferase , Glutathione , Immunoglobulin E , Nasal Obstruction , Oxidative Stress , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Pruritus , Rhinitis , Skin , SneezingABSTRACT
OBJECTIVES: This study is aimed to test the association between the coding sequence functional polymorphism (I105 V) of glutathione S-transferase P gene (GSTP1) and schizophrenia. METHODS: Two hundred fourteen (214) patients with schizophrenia according to the DSM-IV criteria and one hundred ten (110) healthy controls were enrolled in this study. Patients and controls were biologically unrelated age and sex- matched native Koreans. Genotyping for the GSTP1 polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Genotype and allele distributions of the GSTP1 polymorphism in patients with schizophrenia were not significantly different from those of the controls. Comparisons of clinical variables also were not different according to genotype and allele distribution. CONCLUSION: The present study suggests that the GSTP1 polymorphism may not confer susceptibility to development of schizophrenia, at least in the Korean population.
Subject(s)
Humans , Alleles , Clinical Coding , Diagnostic and Statistical Manual of Mental Disorders , Genotype , Glutathione Transferase , Glutathione , SchizophreniaABSTRACT
BACKGROUND AND ackground and Objectives: Smoking has been reported as an important risk factor of laryngeal cancer. Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase P1 (GSTP1) are genes that encode enzymes which are involved in the metabolism of carcinogens in cigarette smoke. In this study, we statistically tested the significances of smoking and genotypes of CYP1A1 and GSTP1 as risk factors of laryngeal cancer. MATERIALS AND METHOD: In this case-control study, 84 pathologically proven laryngeal cancer patients and 168 age- and sex-matched controls were included as the study subjects. Information on smoking habit was collected using a self-administered questionnaire, and CYP1A1 and GSTP1 genotypes were analyzed using PCR-RFLP method. Chi-square test, Student's t-test and conditional logistic analysis were used to test statistical significance. RESULTS: Smoking was turned out to be a significant risk factor of laryngeal cancer both in univariate and multivariate analyses. The CYP1A1 Ile/Ile genotype was significant in the univariate test, but the statistical significance disappeared in the multivariate conditional logistic model including smoking. The odds ratio (95% confidence interval) of GSTP1 A/A genotype for laryngeal cancer was 0.71 (0.38, 1.33), which was not statistically significant. CONCLUSION: Smoking is the most potent risk factor among the three factors, and the genotypes of CYP1A1 and GSTP1 would not be major risk factors for laryngeal cancer in Koreans.