title: Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury.
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±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.
authors.affiliation: 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. Electronic address: barcelos@fcfrp.usp.br.
authors.forename: Gustavo Rafael Mazzaron
authors.initials: GR
authors.lastname: Barcelos
authors.forename: Denise
authors.initials: D
authors.lastname: Grotto
authors.forename: Kátia Cristina
authors.initials: KC
authors.lastname: de Marco
authors.forename: Juliana
authors.initials: J
authors.lastname: Valentini
authors.forename: André van Helvoort
authors.initials: Av
authors.lastname: Lengert
authors.forename: Andréia Ávila Soares
authors.initials: AÁ
authors.lastname: de Oliveira
authors.forename: Solange Cristina
authors.initials: SC
authors.lastname: Garcia
authors.forename: Gilberto Úbida Leite
authors.initials: GÚ
authors.lastname: Braga
authors.forename: Karin
authors.initials: K
authors.lastname: Schläwicke Engström
authors.forename: Ilce Mara de Syllos
authors.initials: IM
authors.lastname: Cólus
authors.forename: Karin
authors.initials: K
authors.lastname: Broberg
authors.forename: Fernando
authors.initials: F
authors.lastname: Barbosa
mesh_terms: D000328:Adult; D001938:Brazil; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D060005:Genotyping Techniques; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000097:blood / Q000235:genetics*; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006197:Hair / Q000737:chemistry; D006801:Humans; D008297:Male; D008630:Mercury Poisoning / Q000097:blood / Q000235:genetics*; D008767:Methylmercury Compounds / Q000032:analysis* / Q000097:blood; D060885:Multiplex Polymerase Chain Reaction; D010084:Oxidation-Reduction / Q000187:drug effects; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D008767:Methylmercury Compounds; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C546365:GCLM protein, human
keywords: Antioxidant status; Fish intake; Gene–environment interactions; Metabolism; Methylmercury; Polymorphisms