Polymorphisms in glutathione-related genes affect methylmercury retention.
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.
Custodio
Hipolito M
HM
Department of Occupational and Environmental Medicine, Lund University Hospital, Lund, Sweden.
Broberg
Karin
K
Wennberg
Maria
M
Jansson
Jan-Håkan
JH
Vessby
Bengt
B
Hallmans
Göran
G
Stegmayr
Birgitta
B
Skerfving
Staffan
S
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
D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D005982:Glutathione Transferase; D005978:Glutathione