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1.
Artigo em Chinês | MEDLINE | ID: mdl-32306671

RESUMO

Objective: To investigate the association between the single nucleotide polymorphisms (SNPS) at rs1695 and rs6591256 in glutathione S-transferase P1 (GSTP1) gene and susceptibility to noise-induced hearing loss in Chinese Han workers exposed to noise. Methods: Using the 1: 1 nested case-control study and taking 6297 workers exposed to noise in a steel plant in Henan province as the cohort study population in July 2019, we screened those who have been exposed to noise for ≥3 years and whose binaural high frequency (3000, 4000, 6000 Hz) average hearing threshold is ≥40 dB (A) into the case group. The control group was selected according to the matching criteria of the same sex, same type of work, and the age difference was not more than 5 years old, and the working age difference was not more than 2 years. 276 subjects were selected into the case group and the control group respectively. The medium and high throughout single nucleotide polymorphism typing technology (SNPscanTM technology) was used to detect the polymorphism of three nucleotide sites of GSR gene, and conditional logistic regression was used to analyze the relationship between single nucleotide polymorphism (SNP) and NIHL, and the relationship between different polymorphic sites and the risk of NIHL after adjusting covariates. After stratification with different cumulative noise exposure (CNE) , Conditional logistic regression analysis was used to analysis the risk of NIHL at different loci. Results: The mean and standard deviation of age of the selected subjects was (40.28±8.00) , the mean and standard deviation of noise-exposed working years was (18.7±8.92) years. The range of noise exposure levels and comulative noise exposure were 80.05-93.35dB (A) and 86.83-107.92 dB (A) ·year, respectively. Compared with the control group, there were no statistically significant differences in age, noise-exposured working years, intensity of noise exposure, CNE, gender, drinking, hypertension prevalence and noise exposure level in the hearing loss group (P>0.05) , while there were statistically difference in smoking, binaural high-frequency average hearing threshold and binaural speech frequency (P<0.05) . After adjusting for smoking, drinking, hypertension and other factors, in the co-dominant model, compared with GGgenotype, the risk of NIHL was higher in rs1002149 GT genotype and rs2251780 GA genotype (OR=1.558, 95%CI: 1.028-2.361; OR=1.550, 95%CI: 1.020-2.355, P<0.05) ; compared with TT/GT genotype, the rs1002149 TT genotype has a higher risk of developing NIHL (OR=1.494, 95%CI: 1.002-2.228, P<0.05) , while rs3779647 genotype had no relationship with the risk of NIHL (P>0.05) . In the equivalent sound level (L(Aeq)) of noise >85 dB (A) stratification, compared with GG genotype, carrying rs1002149 GT genotype and rs2251780 GT genotype has higher risk of nihl (OR=1.801, 95%CI: 1.093-2.967; OR=1.720, 95%CI: 1.050-2.817, P<0.05) . Haplotype analysis of two sites, rs1002149 and rs2251780, was not found to be related to NIIHL susceptibility. Conclusion: The allele G of rs1695 and rs6591256 may be risk factors of NIHL.


Assuntos
Glutationa S-Transferase pi/genética , Perda Auditiva Provocada por Ruído/genética , Ruído Ocupacional , Estudos de Casos e Controles , China , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
2.
Artigo em Chinês | MEDLINE | ID: mdl-32306675

RESUMO

Objective: To investigate the association between the single nucleotide polymorphisms (SNPS) at rs1695 and rs6591256 in glutathione S-transferase P1 (GSTP1) gene and susceptibility to noise-induced hearing loss in Chinese Han workers exposed to noise. Methods: A 1: 2 matched nested case-control study was performed, which based on the cohort of 6297 workers exposed to noise in an iron and steel plant in Henan, China, who were followed up from January 1, 2006 to December 31, 2015. According to the criteria of binaural average high-frequency hearing threshold ≥40 dB, a total of 292 workers were enrolled as hearing loss group; after the adjustment for sex, type of work, age (difference≤5 years) , and working years of noise exposure (difference≤2 years) , according to the criteria of binaural average high-frequency hearing threshold <35 dB, and the speech frequency hearing threshold of any ear at any frequency band ≤25 dB, a total of 584 workers were enrolled as control group. The single nucleotide polymorphisms (SNPs) of rs1695 and rs6591256 in GSTP1 were genotyped by high throughput SNP genotyping assay. Hardy-Weinberg equilibrium of control group was checked. The association between the SNPs at the two loci and susceptibility to NIHL was analyzed. Results: The L(Aeq, 8 h) range of workers exposed to noise was 80.2-98.8 dB (A) . The risk of NIHL in individuals with allele G of rs1695 was 1.291 times of those with allele A (95%CI: 1.042-1.598, P<0.05) . The risk of NIHL in individuals with allele G of rs6591256 was 1.390 times of those with allele A (95%CI: 1.119-1.728, P<0.05) . The risk of NIHL in individuals with AG and GG genotypes of rs6591256 was 1.437 times of those with AA genotype (95%CI: 1.057-1.952, P<0.05) . With the increase of noise exposure duration, individuals with AG and GG genotypes of rs6591256 had a higher risk of NIHL than those with AA genotype (HR=1.273, 95%CI: 1.002-1.616, P<0.05) . Conclusion: The allele G of rs1695 and rs6591256 may be risk factors of NIHL.


Assuntos
Glutationa S-Transferase pi/genética , Perda Auditiva Provocada por Ruído/genética , Ruído Ocupacional , Estudos de Casos e Controles , China , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
3.
PLoS One ; 15(3): e0216147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32155154

RESUMO

BACKGROUND: Fourteen previous meta-analyses have been published to analyze the polymorphisms of individual GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val on breast cancer (BC) risk. However, their meta-analyses did not explore the combined effects of the three genetic polymorphisms on BC risk. In addition, they did not evaluate the credibility of statistically significant associations. Furthermore, a multitude of new articles have been published on these themes, and therefore a meta-analysis and re-analysis of systematic previous meta-analyses were performed to further explore these issues. OBJECTIVES: To determine the association between the individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on breast cancer risk. METHODS: Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were applied to estimate the association between individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on BC risk. To evaluate the credibility of statistically significant associations in the current and previous meta-analyses, we applied the the false-positive report probabilities (FPRP) test and the Venice criteria. RESULTS: 101 publications were selected to evaluate the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms on BC risk. Overall, statistically significant elevated BC risk was found in any individual and combined effects of GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val polymorphisms. However, when we restricted studies only involving with high-quality, matching, HWE, and genotyping examination performed blindly or with quality control, significantly increased BC risk was only found in overall population for GSTM1 null genotype, among all populations, Caucasians, and postmenopausal women for the combined effects of GSTM1 and GSTT1 polymorphisms, and in overall analysis for the combined effects of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms. Further, less-credible positive results were identified when we evaluated the credibility of positive results of the current and previous meta-analyses. CONCLUSIONS: This meta-analysis indicates that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms may be not associated with increased BC risk.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Estudos de Associação Genética , Heterogeneidade Genética , Humanos , Probabilidade , Viés de Publicação , Fatores de Risco
4.
Environ Sci Pollut Res Int ; 27(16): 19375-19382, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32212077

RESUMO

The aim of the study was frequency analysis of GSTM1, GSTT1, and GSTP1 polymorphisms of glutathione S-transferase in the group of patients with prostate cancer and in a control group of healthy individuals. Genomic DNA was isolated; molecular analysis of glutathione S-transferase M1 and T2 polymorphisms was performed using multiplex PCR and RFLP methods. The products of the PCR reaction were then visualized in agarose gel, and a statistical analysis of the results was performed. No statistically significant differences were found in the frequency of glutathione S-transferase polymorphisms between 66 patients with prostate cancer and the control group (64 healthy volunteers). The GSTM1 gene deletion was found in ca. 47% of patients with prostate cancer and in ca. 55% of the controls. The GSTT1 deletion was found in approximately 17% of patients and 14% of the controls. The distribution of GSTP1 Ile/Ile, Ile/Val, and Val/Val polymorphisms was ca. 51.5%, 39%, and 9% in the group of patients and 61%, 34%, and 5% in the control group, respectively. The results indicate that there is no relationship between glutathione S-transferase polymorphisms and prostate cancer in the study group, which is a novelty when compared with the previous work on the role of these genetic variants in the etiology of cancer.


Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Estudos de Casos e Controles , Genótipo , Humanos , Masculino , Polônia , Fatores de Risco
5.
Int J Occup Environ Med ; 11(1): 53-58, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905195

RESUMO

BACKGROUND: Exposure to numerous chemicals, including industrial ones, may result in liver damage. The body susceptibility to the environmental hazards largely depends on the activity of the enzymes in the xenobiotic detoxification system. Function abnormalities of such enzymes due to genetic variations would increase the risk of developing various diseases. OBJECTIVE: To elucidate the relationship between polymorphism in glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and the risk of toxic liver damage in a group of petrochemical workers. METHODS: This study was conducted on 72 workers with toxic liver injury, 156 healthy workers, and 322 healthy individuals without history of occupational exposure to chemicals. Genotyping of the GSTP1 rs1695 gene polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Polymerase chain reaction (PCR) was used to perform genotyping of the GSTM1 and GSTT1 genes polymorphism. RESULTS: There was a significant difference in genotype frequencies of the GSTP1 rs1695 gene polymorphism among the groups studied. The distribution of Val/Val genotype of the GSTP1 rs1695 gene polymorphism had a higher incidence in healthy workers compared with patients with toxic liver damage (p=0.036). No significant association was found between the GSTM1 and GSTT1 polymorphisms and toxic liver damage. CONCLUSION: The GSTP1 rs1695 gene polymorphism can play a protective role in the development of toxic liver damage in petrochemical workers.


Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Fígado/patologia , Exposição Ocupacional/efeitos adversos , Adulto , Estudos de Casos e Controles , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição
6.
Oncology ; 98(4): 243-247, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31958798

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the fourth leading cause of cancer-related deaths worldwide. HCC cases are two to four times more common in males than in females, and the highest incidence is found in Asia and Sub-Saharan Africa. This gender disparity is the result of different behavioral risk factors, such as smoking and drinking alcohol. Glutathione S-Transferase P1 (GSTP1) is an enzyme that is involved in the detoxification of carcinogenic electrophiles. GSTP1 codon 105 in exon 5 and codon 114 in exon 6 polymorphisms result in decreased enzyme detoxification activity, which is the cause of many cancers. OBJECTIVES: This study aims to investigate the associations between GSTP1 polymorphism, HCC patients, and the risk factors for HCC. It is hoped that this research will provide useful knowledge on the effects of genetic GSTP1 polymorphism in Thai HCC patients. METHODS: DNA from 44 Thai HCC patients and 52 healthy controls was analyzed for GSTP1 exon 5 and exon 6 polymorphisms by PCR-RFLP. The associations between GSTP1 polymorphism, the control group, and clinicopathological parameters were determined. RESULTS: The results show that GSTP1 exon 6 polymorphism genotypes (C/T) were correlated with an increased risk of HCC susceptibility (OR = 4.40). Moreover, exon 6 polymorphism genotypes (C/T) were associated with the gender of patients (p = 0.015), but no relationships were found between GSTP1 exon 5 polymorphism and the clinicopathological data of patients. CONCLUSIONS: The results suggest that the GSTP1 exon 6 polymorphism genotype was associated with an increase in the risk of HCC in male patients and that it tended to be related to cancer differentiation. No association was found between GSTP1 exon 5 polymorphism and the risk of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Éxons , Glutationa S-Transferase pi/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Risco
7.
J Dermatolog Treat ; 31(3): 300-308, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30897007

RESUMO

The aim of this study was to investigate if aloe polysaccharide (AP) has the repairing effect on ultraviolet b (UVB) injured nerve cells. The study applied BALB/c female mice as animal model, and NFG-activated PC12 cells as cell model of skin nerve. The cell viability was detected by MTT assay, and cell apoptosis was detected by TUNEL (TdT-mediated dUTP nick-end labeling) and Annexin-V/PI assay, and cell-cycle status in different groups were observed via flow cytometry (FCM). Enzyme-linked immunosorbent assay (ELISA) was applied to analyze oxidative stress and anti-oxidative ability in each group. Real-time PCR and western blot were used to detect the expression levels of Bax, Bcl-2, Caspase-3, Cyclin D1, Keap1, Nrf2, GCLC, and GSTP1. The results showed obvious inhibition of cell viability and cell-cycle progression and promotion of cell apoptosis by UVB irradiation through inducing oxidative stress. In AP treated groups, cell viability and proliferation could be markedly improved and cell apoptosis inhibited with higher anti-oxidative capability and up-regulated expression of Keap1, Nrf2, GCLC, and GSTP1. It suggested that AP was able to repair UVB induced injury on NGF activated skin neural cell PC12, probably through Keap1/Nrf2/ARE signal pathway.


Assuntos
Aloe/metabolismo , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ciclina D1/metabolismo , Feminino , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator de Crescimento Neural/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos da radiação
8.
Nat Chem Biol ; 16(2): 150-159, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31768034

RESUMO

Covalent probes serve as valuable tools for global investigation of protein function and ligand binding capacity. Despite efforts to expand coverage of residues available for chemical proteomics (e.g., cysteine and lysine), a large fraction of the proteome remains inaccessible with current activity-based probes. Here, we introduce sulfur-triazole exchange (SuTEx) chemistry as a tunable platform for developing covalent probes with broad applications for chemical proteomics. We show modifications to the triazole leaving group can furnish sulfonyl probes with ~5-fold enhanced chemoselectivity for tyrosines over other nucleophilic amino acids to investigate more than 10,000 tyrosine sites in lysates and live cells. We discover that tyrosines with enhanced nucleophilicity are enriched in enzymatic, protein-protein interaction and nucleotide recognition domains. We apply SuTEx as a chemical phosphoproteomics strategy to monitor activation of phosphotyrosine sites. Collectively, we describe SuTEx as a biocompatible chemistry for chemical biology investigations of the human proteome.


Assuntos
Sondas Moleculares/química , Proteômica/métodos , Enxofre/química , Triazóis/química , Tirosina/análise , Tirosina/química , Células A549 , Sítios de Ligação , Flúor/química , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismo , Células HEK293 , Humanos , Sondas Moleculares/síntese química , Fosforilação , Fosfotirosina/química , Fosfotirosina/metabolismo , Domínios Proteicos , Processamento de Proteína Pós-Traducional , Ácidos Sulfínicos/química , Tirosina/metabolismo
9.
Ecotoxicol Environ Saf ; 189: 109975, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31787382

RESUMO

Coal plants represent one of the main sources of environmental pollution due to the combustion process of this mineral and the consequent release of gases and particles which, in significant quantities, can lead to a potential risk to health and the environment. The susceptibility of individuals to the genotoxic effects of coal mining can be modulated by genetic variations in the xenobiotic detoxification and DNA repair processes. The aim of this study was to evaluate if xenobiotic metabolism polymorphism, base excision repair polymorphisms and non-homologous end joining repair polymorphism, could modify individual susceptibility to genomic instability and epigenetic alterations induced in workers by occupational exposure to coal. In this study, polymerase chain reaction was used to examine the polymorphic sites. The sample population comprising 70 coal mine workers and 71 workers non-exposed to coal. Our results demonstrated the effect of individual genotypes on different biomarkers evaluated. Significant decrease in % of global DNA methylation were observed in CYP1A1 Val/- exposed individuals compared to CYP1A1 Ile/Ile individuals. Coal workers who carried the XRCC4 Ile/Ile genotype showed decrease NBUD frequencies, while the XRCC4 Thr/- genotype was associated with decrease in Buccal micronucleus cells for the group not exposed. No influence of GSTM1 null, GSTT1 null, GSTP1 Ile105Val, hOGG1 Ser326Cys, XRCC1 Arg194Trp polymorphisms was observed. Thus, the current study reinforces the importance of considering the effect of metabolizing and repair variant genotypes on the individual susceptibility to incorporate DNA damage, as these processes act in a coordinated manner to determine the final response to coal exposure.


Assuntos
Minas de Carvão , Carvão Mineral/toxicidade , Dano ao DNA , Metilação de DNA , Exposição Ocupacional , Polimorfismo Genético , Homeostase do Telômero , Adolescente , Adulto , Idoso , Citocromo P-450 CYP1A1/genética , Reparo do DNA , Proteínas de Ligação a DNA/genética , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Xenobióticos/metabolismo , Adulto Jovem
10.
Bull Exp Biol Med ; 167(6): 767-770, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31677022

RESUMO

The correlation of gene polymorphisms rs4025935 (large deletion), rs1695 (313A>G), rs71748309 (large deletion), and rs1800566 (609C>T) of GSTM1, GSTT1, and NQO1 genes encoding glutathione-S-transferases (GST) M1, P1, and T1 and NADPH-quinone oxidoreductase with the risk of development of classical Ph-negative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) was studied in the Caucasian ethnicity population of Vyatka region of the Russian Federation. It was found that NQO1*609T allele, NQO1*609T genotypes, and homozygous carriage of a deletion (null) allele of GSTT1 gene are associated with the risk of development of myeloproliferative neoplasms (OR=1.29, 95%CI=1.02-1.64, p=0.04; OR=1.39, 95%CI=1.04-1.85, p=0.03; and OR=1.48, 95%CI=1.03-2.12, p=0.03, respectively). However, no influence of GSTM1 and GSTP1 gene polymorphisms on the risk of development of myeloproliferative disorders was registered.


Assuntos
Glutationa Transferase/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , Polimorfismo Genético , Xenobióticos/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biotransformação/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Deleção de Genes , Glutationa S-Transferase pi/genética , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/metabolismo , Cromossomo Filadélfia , Polimorfismo de Nucleotídeo Único , Adulto Jovem
11.
Int J Chron Obstruct Pulmon Dis ; 14: 2081-2088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564855

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by incomplete reversible airflow limitation, which is associated with emphysema and chronic inflammation. Oxidative/antioxidant imbalance is one of the mechanisms of the current pathogenesis of COPD and several recent studies have attempted to uncover genetic causes of COPD and its progression. GST, HO-1, and SOD-3 are important susceptibility genes related to COPD. Methods: A total of 300 blood samples were included in two groups: Control group and COPD group. We genotyped 4 single nucleotide polymorphisms (SNPs) from these 3 genes in 150 COPD patients and 150 controls to analyze genetic polymorphisms and interactions with COPD-related quantitative traits using correlation analysis and multivariate logistic regression analysis. Results: The results indicated that genotype distributions and allele frequencies of GSTP1, HO-1, and SOD-3 were significantly different between the COPD and the control group, while there is no correlation between the polymorphism of GSTP1, HO-1, SOD3, and the different stages of COPD. Furthermore, multivariate logistic regression analysis indicated that COPD GSTP1-exon5 SNP and HO-1 (GT)n SNP are high-risk factors for COPD and there was interaction between GSTP1 exon5 SNPS and HO-1 (GT)n SNP. More important, the genotypes, AG, GG of GSTP1 exon5 and L/M*S, L/L of HO-1 (GT)n associated with increased 8-iso-prostaglandin F (2 alpha) (8-iso-PGF2) and malondialdehyde (MDA) concentration and decreased catalase (CAT) activity. Conclusion: Collectively, this study shows that genetic polymorphisms of GSTP1, HO-1, and SOD-3 are associated with COPD susceptibility.


Assuntos
Glutationa S-Transferase pi/genética , Heme Oxigenase-1/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Superóxido Dismutase/genética , Idoso , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/enzimologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Capacidade Vital
12.
Medicine (Baltimore) ; 98(41): e17487, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593112

RESUMO

To analyze the association between glutathione S-transferases polymorphisms and the risk of cervical lesions.Case-control studies focusing on the association between glutathione S-transferase polymorphisms and the risk of cervical lesions were collected from the PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang databases from inception to August 2018. Pooled odds ratios and 95% confidence intervals were employed to evaluate the strength of the association. Subgroup analysis and sensitivity analysis were used to test the potential discrepancy and robustness, respectively.A total of 30 studies comprising 3961 patients and 4726 healthy controls satisfied the inclusion criteria. Of these, 6 studies contained information about GSTP1, 27 studies contained information about GSTM1, and 22 studies contained information about GSTT1. Our results supported that there was no statistical association between GSTP1 polymorphism and the risk of cervical lesions (odds ratio [OR] = 1.08, P = .40). The GSTM1 null variant showed increased susceptibility to cervical lesions (OR = 1.45, P < .001). Subgroup analysis revealed that the GSTM1 null variant caused cervical lesions among HPV infection cases (OR = 1.69, P = .02) and among the Chinese and Indian populations (OR = 2.24 and OR = 1.87, respectively, P < .001). The GSTT1 null variant increased the risk of cervical lesions in smokers (OR = 1.52, P = .03). The GSTT1 null genotype was also related to high-grade intraepithelial neoplasia (HSIL) and cervical cancer risk (OR = 1.30 and OR = 1.78, respectively, P < .05).The GSTM1 null variant caused cervical lesions, especially among HPV infection cases and among the Chinese and Indian populations. The GSTT1 null variant increased the risk of cervical lesions in smokers and was also related to HISL and cervical cancer risk.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias do Colo do Útero/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/virologia , China , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Humanos , Índia , Pessoa de Meia-Idade , Razão de Chances , Infecções por Papillomavirus/genética , Fatores de Risco , Neoplasias do Colo do Útero/virologia
13.
BMC Cancer ; 19(1): 991, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646988

RESUMO

BACKGROUND: The glutathione S-transferases (GSTs) are a superfamily of phase II detoxifying enzymes that inactivates a wide variety of potential carcinogens through glutathione conjugation. Polymorphic changes in the GST genes have been reported to be associated with increased susceptibility to cancer development and anticancer drug resistance. In this study, we investigated the association between genetic variants in GSTM1 and GSTP1 and patients' clinicopathological parameters. The prognostic values of such associations were evaluated among bladder cancer patients. METHODS: Genotyping of GSTM1 and GSTP1 in bladder cancer patients was assessed using polymerase chain reaction followed by DNA sequencing. Overall survival was estimated using the Kaplan-Meier method and multiple logistic regression and correlation analysis were performed. RESULTS: The GSTM1 null genotype was significantly associated with poor overall survival compared with the wild-type GSTM1 genotype. There was a trend towards better overall survival in patients with wild-type GSTP1 allele (AA) compared with GSTP1 (AG/GG) genotype. Interestingly, Kaplan-meier survival curve for GSTM1 null patients adjusted for sub-cohort with amplified HER2 gene showed poor survival compared with the GSTM1 null/ non-amplified HER2 gene. Also the same population when adjusted with HER2 protein expression, data showed poor survival for patients harboring GSTM1 null/high HER2 protein expression compared with low protein expression. CONCLUSION: This study focuses on the impact of GSTM1 null genotype on bladder cancer patients' outcome. Further investigations are required to delineate the underlying mechanisms of combined GSTM-/- and HER2 status in bladder cancer.


Assuntos
Predisposição Genética para Doença/genética , Variação Genética , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Receptor ErbB-2/metabolismo , Arábia Saudita , Análise de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
14.
Int J Rheum Dis ; 22(12): 2119-2124, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637859

RESUMO

AIM: It is commonly assumed that a genetically determined polymorphism of xenobiotic biotransformation plays a particular role in the development of such disease entities in which chemical compounds and environmental pollutants are relevant etiologic factors. Systemic sclerosis (SSc, scleroderma) belongs to diseases of connective tissue, characterized by chronic inflammation developing on an autoimmune background. The current state of knowledge on the etiopathogenesis of autoimmune diseases indicates the existence of many factors affecting the development of the disease, including factors of the external environment. Considering all the above, a study on a role of genetic polymorphisms of glutathione S-transferase has been undertaken in which predisposition to SSc in a Polish population was assessed. METHODS: The study was carried out in 161 subjects: 61 patients with SSc and 100 healthy volunteers. A determination of the polymorphism of GSTM1 and GSTT1 was performed with a multiplex PCR (polymerase chain reaction). The GSTP1 polymorphism was determined by using the PCR restriction fragment length polymorphism. RESULTS: The risk of developing SSc was 3-fold higher for persons with the null GSTM1 and GSTT1 genotypes (odds ratio [OR] = 3.3; P = .0051). The risk for SSc was also demonstrated to be over 2.5-fold greater in the GSTP1 Ile/Val genotype individuals (OR = 2.62; P = .0037). Carriers of the GSTP1 Val variant allele had a greater than 2-fold increase in SSc risk (OR = 2.41; P = .0006). CONCLUSION: The genetic polymorphism of glutathione S-transferase may affect the risk of SSc in a Polish population.


Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo Genético , Escleroderma Sistêmico/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polônia/epidemiologia , Medição de Risco , Fatores de Risco , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/enzimologia , Escleroderma Sistêmico/epidemiologia , Adulto Jovem
15.
Asian Pac J Cancer Prev ; 20(10): 3093-3100, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31653159

RESUMO

AIM: CAPOX treatment in CRC patients was reported to cause several dose-limiting toxicities, and are found responsible for treatment interruption or even discontinuation. Therefore there is a critical need for identifying the predictive biomarkers for such toxicities to prevent them. The aim of our present study is to find the influence of DPYD*9A, DPYD*6 and GSTP1 ile105val gene polymorphisms on CAPOX treatment-associated toxicities in south Indian patients with CRC. PATIENTS AND METHODS: We have recruited 145 newly diagnosed and treatment naive CRC patients in the study. Each Patient received a standard treatment schedule of oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. 5 ml of the venous blood was collected from each patient and genomic DNA extraction and genotyping. The genotyping analysis of the selected genetic polymorphisms was carried out by real-time PCR using TaqMan SNP genotyping assays obtained from applied biosystems. RESULTS: The major dose-limiting toxicities observed with CAPOX treatment were thrombocytopenia, HFS and PN. DPYD*9A carries were found to be at higher risk for HFS, diarrhoea and thrombocytopenia when compared to patients with wild allele. No significant association was found between DPYD*6, GSTP1 ile105val polymorphisms and CAPOX related toxicities except for thrombocytopenia. CONCLUSION: A significant association was observed between DPYD*9A polymorphism and CAPOX induced dose-limiting toxicities strengthening its role as a predictive biomarker.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Di-Hidrouracila Desidrogenase (NADP)/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glutationa S-Transferase pi/genética , Polimorfismo Genético , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Prognóstico
16.
Asian Pac J Cancer Prev ; 20(9): 2707-2714, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31554367

RESUMO

Aim: In this case control study involving, 220 human subjects; polymorphisms in xenobiotic metabolizing genes (GST-M1, -T1 and -P1) and their association to lung cancer risk is being analysed among smokers and nonsmokers. GSTM1 or GSTT1 gene polymorphism and amino acid changes in GSTP1 have been correlated and may be associated to lung cancer risk. Other factor includes exposure to environmental pollutants and life style choices. We have explored gene-gene and gene-environment interaction in the aetiology of lung cancer risk among north Indian population. Patients and Methods: For the study we have collected 120 lung cancer patient blood samples from Kamala Nehru Memorial Cancer Hospital, Allahabad, Uttar Pradesh and 100 matched controls. DNA was isolated and GST-M1 and - T1 genotyping were assessed by multiplex PCR whereas the GSTP1 polymorphism was analysed using restriction fragment length polymorphism. The risk of lung carcinogenesis was assessed using logistic regression analysis calculating the odd ratio (OR) with 95% confidence interval (CI). Results: The risk of lung carcinogenesis was three fold higher for null GSTT1 (OR=3.045, 95%CI=1.750-5.301, p-value <0.001) genotype; whereas other two types; GSTM1 (OR= 1.342, 95% CI=0.788-2.284, p-value=0.270) and GSTP1 (OR=0.806, 95% CI=0.526-1.236, p-value=0.323) showed no association to lung cancer susceptibility respectively. Smokers diagnosed with lung cancer had more null genotypes for GSTT1 (OR=4.773, 95%CI=1.939-11.751, p<0.001). The 'at risk' genotype combination GSTM1 (null) /GSTT1 (null) (OR=1.76, 95%CI; 0.920-3.370, p-value=0.03) showed increased susceptibility to lung cancer risk. The genotype combination of GSTT1 (null)/GSTP1 (Ile/Ile) (p=0.009) was associated with increased lung cancer risk. Conclusion: The results of this study suggest that; GSTT1 null genotype were more susceptible for lung cancer risk and smoking increases the susceptibility for lung cancer several folds among the North Indian population. Gene-gene interaction for null genotypes of GSTM1 and GSTT1 were correlated with higher risk of having lung cancer.


Assuntos
Biomarcadores Tumorais/genética , Epistasia Genética , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo Genético , Carcinoma de Pequenas Células do Pulmão/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto Jovem
17.
J Genet ; 982019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31544773

RESUMO

This study aims to analyse the potential relationship between single-nucleotide polymorphism (SNPs) in trace element related metabolic genes GSTM3, GSTP1, GPX1 and NKG2D and the risk of gastric cancer. A case-control study was conducted in the hospital of Xianyou, Fujian, China. In this study, a total of 299 patients with histopathological diagnosis in gastric cancer and 295 healthy control subjects were involved. Association between the SNPs in trace element-related metabolic genes and gastric cancer risk was analysed using the unconditional logistic regression model. No relationship was found between the SNPs of GSTM3 and GPX1 genes and gastric cancer risk. However, the risk of gastric cancer is related to the SNPs of NKG2D gene (rs1049174). Patients who carry the rs1049174 GG genotype have a higher incidence of the gastric cancer and a multivariate odds ratio (OR) of 1.85 (95% confidence intervals (CI): 1.02-3.38). Through haplotype analysis, two haplotypes (i.e. A_rs1746123-T_rs10431294-G_rs1049174 and T_rs1746123-T_rs10431294-C_rs1049174), OR of 0.29 (95% CI: 0.15-0.56) and 0.33, (95% CI: 0.22-0.50), respectively, were found to have lower incidence of gastric cancer. Meanwhile, another two haplotypes (T_rs1746123-C_rs10431294-C_rs1049174 and T_rs1746123-T_rs10431294-G_rs1049174), OR of 1.81 (95% CI: 1.40-2.34) and 3.09 (95% CI: 2.30-4.16), respectively, were found to have a higher incidence of gastric cancer. Further, no influence of the haplotype on the risk of cardia gastric cancer was found. However, the haplotype T_rs1746123-T_rs10431294-C_rs1049174 had lower incidence of noncardia gastric cancer by 46%. Our data showed that polymorphisms of trace element-related metabolic genes are important in gastric cancer pathology.


Assuntos
Neoplasias Gástricas/genética , Oligoelementos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença/epidemiologia , Glutationa Peroxidase/sangue , Glutationa Peroxidase/genética , Glutationa S-Transferase pi/sangue , Glutationa S-Transferase pi/genética , Glutationa Transferase/sangue , Glutationa Transferase/genética , Haplótipos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Subfamília K de Receptores Semelhantes a Lectina de Células NK/sangue , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias Gástricas/sangue
18.
Prostate ; 79(14): 1705-1714, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31433512

RESUMO

BACKGROUND: We identify and validate accurate diagnostic biomarkers for prostate cancer through a systematic evaluation of DNA methylation alterations. MATERIALS AND METHODS: We assembled three early prostate cancer cohorts (total patients = 699) from which we collected and processed over 1300 prostatectomy tissue samples for DNA extraction. Using real-time methylation-specific PCR, we measured normalized methylation levels at 15 frequently methylated loci. After partitioning sample sets into independent training and validation cohorts, classifiers were developed using logistic regression, analyzed, and validated. RESULTS: In the training dataset, DNA methylation levels at 7 of 15 genomic loci (glutathione S-transferase Pi 1 [GSTP1], CCDC181, hyaluronan, and proteoglycan link protein 3 [HAPLN3], GSTM2, growth arrest-specific 6 [GAS6], RASSF1, and APC) showed large differences between cancer and benign samples. The best binary classifier was the GAS6/GSTP1/HAPLN3 logistic regression model, with an area under these curves of 0.97, which showed a sensitivity of 94%, and a specificity of 93% after external validation. CONCLUSION: We created and validated a multigene model for the classification of benign and malignant prostate tissue. With false positive and negative rates below 7%, this three-gene biomarker represents a promising basis for more accurate prostate cancer diagnosis.


Assuntos
Biomarcadores Tumorais , Metilação de DNA/genética , Neoplasias da Próstata/classificação , Neoplasias da Próstata/patologia , DNA/isolamento & purificação , Epigênese Genética , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/genética , Glutationa S-Transferase pi/análise , Glutationa S-Transferase pi/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Neoplasias da Próstata/química , Proteoglicanas/análise , Proteoglicanas/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Gene ; 719: 144077, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31454540

RESUMO

BACKGROUND: Glutathione S-transferases (GSTs) contain a series of critical enzymes regulating proliferation or apoptosis in the tumor microenvironment. Data from publications about the correlation between Glutathione S-transferase Pi 1 (GSTP1) gene 313 A/G (rs1695) polymorphism and bladder caner (BCa) remained controversial. To explore the exact correlation between this polymorphism and the development of BCa, we carried out this study. MATERIALS AND METHODS: All relevant publications from Pubmed, Web of Science, Cochrane Library, PMC, Embase and Wanfang databases (from building to March 30th, 2019) were retrieved. This meta-analysis was carried out by utilizing STATA software. RESULTS: 34 case-control studies with 15,704 participants recruiting 7236 BCa patients and 8468 healthy controls were ultimately analyzed in our study. The pooling results indicated that GSTP1 gene 313 A/G (rs1695) polymorphism was obviously related to BCa (GG vs AA: OR = 1.33, 95%CI = 1.04-1.69). Similar results were found in the association between this polymorphism and transitional cell carcinoma (TCC) risk (GG vs AA: OR = 1.95, 95%CI = 1.18-3.23). Furthermore, we revealed an increased association between the GG genotype and BCa in Asians (GG vs AA: OR = 2.04, 95%CI = 1.09-3.79), while no correlation was revealed in Caucasians. As to different tumor grades or stages, this polymorphism was considered to elevate low grade BCa development and null results were uncovered with high grade BCa. CONCLUSION: This study indicated that GSTP1 gene 313 A/G (rs1695) polymorphism increased the susceptibility to BCa, particularly to TCC. In addition, this study found that this polymorphism was obviously related to elevated BCa risk in Asian population and also increased low grade BCa risk. Results based on the five genetic models indicated that GSTP1 G-allele might be the susceptibility gene and GG genotype might be the susceptibility genotype.


Assuntos
Predisposição Genética para Doença , Glutationa S-Transferase pi/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/genética , Estudos de Casos e Controles , Genótipo , Humanos
20.
Genes (Basel) ; 10(9)2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450602

RESUMO

(1) Background: A simulation approach for prostate cancer (PrCa) with a prostate-specific antigen (PSA) test incorporating genetic information provides a new avenue for the development of personalized screening for PrCa. Going by the evidence-based principle, we use the simulation method to evaluate the effectiveness of mortality reduction resulting from PSA screening and its utilization using a personalized screening regime as opposed to a universal screening program. (2) Methods: A six-state (normal, over-detected, low-grade, and high-grade PrCa in pre-clinical phase, and low-grade and high-grade PrCa in clinical phase) Markov model with genetic and PSA information was developed after a systematic review of genetic variant studies and dose-dependent PSA studies. This gene‒PSA-guided model was used for personalized risk assessment and risk stratification. A computer-based simulated randomized controlled trial was designed to estimate the reduction of mortality achieved by three different screening methods, personalized screening, universal screening, and a non-screening group. (3) Results: The effectiveness of PrCa mortality reduction for a personalized screening program compared to a non-screening group (22% (9%‒33%)) was similar to that noted in the universal screening group (20% (7%‒21%). However, a personalized screening program could dispense with 26% of unnecessary PSA testing, and avoid over-detection by 2%. (4) Conclusions: Gene‒PSA-guided personalized screening for PrCa leads to fewer unnecessary PSA tests without compromising the benefits of mortality reduction (as happens with the universal screening program).


Assuntos
Simulação por Computador , Testes Genéticos/métodos , Polimorfismo de Nucleotídeo Único , Medicina de Precisão/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/genética , Metilação de DNA , Testes Genéticos/normas , Glutationa S-Transferase pi/genética , Humanos , Fator de Crescimento Insulin-Like I/genética , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/normas , Neoplasias da Próstata/sangue , Distribuição Aleatória
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