title: Polymorphisms in glutathione-related genes affect methylmercury retention.
abstract: Methylmercury is eliminated from the human body as glutathione (GSH) conjugates. GSH production is mediated by glutamyl-cysteine ligase (GCL) and conjugation by glutathione S-transferases (GST). In this study, the authors tested whether polymorphisms in GCL and GST genes modify methylmercury retention. Erythrocyte mercury concentration (EryHg), plasma polyunsaturated fatty acids (PPUFA), and genotype for GCLC, GCLM, GSTA1, GSTM1, GSTP1, and GSTT1 were determined in 365 individuals. A general linear model was developed for analyzing whether genotype modified the regression of EryHg on PPUFA. The presence of one variant allele for either GCLC-129 or GSTP1-114 was associated with higher EryHg and steeper regression slope. No similar trends were shown for GCLM, GSTA1, GSTM1, or GSTT1. These findings indicate that GCLC polymorphisms that affect GSH production also affect methylmercury retention, and that GSTP1 may play a role in conjugating methylmercury with GSH.
authors.affiliation: Department of Occupational and Environmental Medicine, Lund University Hospital, Lund, Sweden.
authors.forename: Hipolito M
authors.initials: HM
authors.lastname: Custodio
authors.forename: Karin
authors.initials: K
authors.lastname: Broberg
authors.forename: Maria
authors.initials: M
authors.lastname: Wennberg
authors.forename: Jan-Håkan
authors.initials: JH
authors.lastname: Jansson
authors.forename: Bengt
authors.initials: B
authors.lastname: Vessby
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Birgitta
authors.initials: B
authors.lastname: Stegmayr
authors.forename: Staffan
authors.initials: S
authors.lastname: Skerfving
mesh_terms: D000328:Adult; D000368:Aged; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D004912:Erythrocytes; D005260:Female; D005838:Genotype; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008767:Methylmercury Compounds / Q000493:pharmacokinetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D005982:Glutathione Transferase; D005978:Glutathione