Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury
Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was...
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| Veröffentlicht in: | The Science of the total environment Jg. 463-464; S. 319 - 325 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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Elsevier B.V
01.10.2013
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| ISSN: | 0048-9697, 1879-1026, 1879-1026 |
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| Abstract | Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48±36μg/L and 14±10μg/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood β=−0.32, p=0.017; and hair β=−0.33; p=0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (β=0.20; p=0.017) and hair Hg (hair β=0.20; p=0.013). Exposure to MeHg altered antioxidant status (CAT: β=−0.086; GSH: β=−0.12; GPx: β=−0.16; all p<0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects.
•Study subjects are highly exposed to methylmercury via fish intake.•Exposure to methylmercury leads to disturbances of antioxidant status.•Polymorphisms of GSH-related genes may modulate mercury bodyburden.•Genetic effects were seen also on parameters of antioxidant status. |
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| AbstractList | Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48±36 μg/L and 14±10 μg/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood β=-0.32, p=0.017; and hair β=-0.33; p=0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (β=0.20; p=0.017) and hair Hg (hair β=0.20; p=0.013). Exposure to MeHg altered antioxidant status (CAT: β=-0.086; GSH: β=-0.12; GPx: β=-0.16; all p<0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects. Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TagMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48 +/- 36 mu g/L and 14 +/- 10 mu g/g. Persons with the GCLM-588 IT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood beta = -0.32, p = 0.017; and hair beta = -0.33; p = 0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (beta = 0.20; p = 0.017) and hair Hg (hair beta = 0.20; p = 0.013). Exposure to MeHg altered antioxidant status (CAT:beta = -0.086; GSH:beta = -0.12; GPx:beta = -0.16; all p < 0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects. (C) 2013 Elsevier BY. All rights reserved. Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48±36μg/L and 14±10μg/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood β=−0.32, p=0.017; and hair β=−0.33; p=0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (β=0.20; p=0.017) and hair Hg (hair β=0.20; p=0.013). Exposure to MeHg altered antioxidant status (CAT: β=−0.086; GSH: β=−0.12; GPx: β=−0.16; all p<0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects. Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48±36μg/L and 14±10μg/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood β=−0.32, p=0.017; and hair β=−0.33; p=0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (β=0.20; p=0.017) and hair Hg (hair β=0.20; p=0.013). Exposure to MeHg altered antioxidant status (CAT: β=−0.086; GSH: β=−0.12; GPx: β=−0.16; all p<0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects. •Study subjects are highly exposed to methylmercury via fish intake.•Exposure to methylmercury leads to disturbances of antioxidant status.•Polymorphisms of GSH-related genes may modulate mercury bodyburden.•Genetic effects were seen also on parameters of antioxidant status. Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48±36 μg/L and 14±10 μg/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood β=-0.32, p=0.017; and hair β=-0.33; p=0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (β=0.20; p=0.017) and hair Hg (hair β=0.20; p=0.013). Exposure to MeHg altered antioxidant status (CAT: β=-0.086; GSH: β=-0.12; GPx: β=-0.16; all p<0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects.Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48±36 μg/L and 14±10 μg/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood β=-0.32, p=0.017; and hair β=-0.33; p=0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (β=0.20; p=0.017) and hair Hg (hair β=0.20; p=0.013). Exposure to MeHg altered antioxidant status (CAT: β=-0.086; GSH: β=-0.12; GPx: β=-0.16; all p<0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects. Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48 plus or minus 36 mu g/L and 14 plus or minus 10 mu g/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood beta =-0.32, p =0.017; and hair beta =-0.33; p =0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood ( beta =0.20; p =0.017) and hair Hg (hair beta =0.20; p =0.013). Exposure to MeHg altered antioxidant status (CAT: beta =-0.086; GSH: beta =-0.12; GPx: beta =-0.16; all p <0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects. |
| Author | Schläwicke Engström, Karin Grotto, Denise Garcia, Solange Cristina Broberg, Karin Braga, Gilberto Úbida Leite Valentini, Juliana de Marco, Kátia Cristina Cólus, Ilce Mara de Syllos Oliveira, Andréia Ávila Soares de Lengert, André van Helvoort Barcelos, Gustavo Rafael Mazzaron Barbosa, Fernando |
| Author_xml | – sequence: 1 givenname: Gustavo Rafael Mazzaron surname: Barcelos fullname: Barcelos, Gustavo Rafael Mazzaron email: barcelos@fcfrp.usp.br organization: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil – sequence: 2 givenname: Denise surname: Grotto fullname: Grotto, Denise organization: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil – sequence: 3 givenname: Kátia Cristina surname: de Marco fullname: de Marco, Kátia Cristina organization: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil – sequence: 4 givenname: Juliana surname: Valentini fullname: Valentini, Juliana organization: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil – sequence: 5 givenname: André van Helvoort surname: Lengert fullname: Lengert, André van Helvoort organization: Department of General Biology, Center for Biological Sciences, State University of Londrina, Rodovia Celso Garcia Cid km 380, CEP 86051-990, Londrina, Paraná, Brazil – sequence: 6 givenname: Andréia Ávila Soares de surname: Oliveira fullname: Oliveira, Andréia Ávila Soares de organization: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil – sequence: 7 givenname: Solange Cristina surname: Garcia fullname: Garcia, Solange Cristina organization: School of Pharmacy, Federal University of Rio Grande do Sul, Avenida Ipiranga, 2752, CEP 96610-000, Porto Alegre, Brazil – sequence: 8 givenname: Gilberto Úbida Leite surname: Braga fullname: Braga, Gilberto Úbida Leite organization: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil – sequence: 9 givenname: Karin surname: Schläwicke Engström fullname: Schläwicke Engström, Karin organization: Division of Occupational and Environmental Medicine, Lund University Hospital, 221 85, Lund, Sweden – sequence: 10 givenname: Ilce Mara de Syllos surname: Cólus fullname: Cólus, Ilce Mara de Syllos organization: Department of General Biology, Center for Biological Sciences, State University of Londrina, Rodovia Celso Garcia Cid km 380, CEP 86051-990, Londrina, Paraná, Brazil – sequence: 11 givenname: Karin surname: Broberg fullname: Broberg, Karin organization: Division of Occupational and Environmental Medicine, Lund University Hospital, 221 85, Lund, Sweden – sequence: 12 givenname: Fernando surname: Barbosa fullname: Barbosa, Fernando organization: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23827356$$D View this record in MEDLINE/PubMed |
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| Copyright | 2013 Elsevier B.V. Copyright © 2013 Elsevier B.V. All rights reserved. |
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| DOI | 10.1016/j.scitotenv.2013.06.029 |
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| Title | Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury |
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