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Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury

Mazzaron Barcelos, Gustavo Rafael ; Grotto, Denise ; de Marco, Katia Cristina ; Valentini, Juliana ; Lengert, Andre van Helvoort ; Soares de Oliveira, Andreia Avila ; Garcia, Solange Cristina ; Leite Braga, Gilberto Ubida ; Engström, Karin LU and de Syllos Colus, Ilce Mara , et al. (2013) In Science of the Total Environment 463. p.319-325
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antioxidant status, Fish intake, Gene-environment interactions, Metabolism, Methylmercury, Polymorphisms
in
Science of the Total Environment
volume
463
pages
319 - 325
publisher
Elsevier
external identifiers
  • wos:000325831200037
  • scopus:84880003315
  • pmid:23827356
ISSN
1879-1026
DOI
10.1016/j.scitotenv.2013.06.029
language
English
LU publication?
yes
id
9aafed8a-7f16-45a0-8b1d-063cdc7e5b8b (old id 4160104)
date added to LUP
2016-04-01 10:45:40
date last changed
2022-03-19 23:46:56
@article{9aafed8a-7f16-45a0-8b1d-063cdc7e5b8b,
  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 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 &lt; 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.}},
  author       = {{Mazzaron Barcelos, Gustavo Rafael and Grotto, Denise and de Marco, Katia Cristina and Valentini, Juliana and Lengert, Andre van Helvoort and Soares de Oliveira, Andreia Avila and Garcia, Solange Cristina and Leite Braga, Gilberto Ubida and Engström, Karin and de Syllos Colus, Ilce Mara and Broberg Palmgren, Karin and Barbosa, Fernando Jr.}},
  issn         = {{1879-1026}},
  keywords     = {{Antioxidant status; Fish intake; Gene-environment interactions; Metabolism; Methylmercury; Polymorphisms}},
  language     = {{eng}},
  pages        = {{319--325}},
  publisher    = {{Elsevier}},
  series       = {{Science of the Total Environment}},
  title        = {{Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury}},
  url          = {{http://dx.doi.org/10.1016/j.scitotenv.2013.06.029}},
  doi          = {{10.1016/j.scitotenv.2013.06.029}},
  volume       = {{463}},
  year         = {{2013}},
}