Polymorphisms in Glutathione-Related Genes Affect Methylmercury Retention |
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| Authors: | Hipolito M Custodio Karin Broberg Maria Wennberg Jan-Håkan Jansson Bengt Vessby Göran Hallmans |
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| Institution: | 1. Department of Occupational and Environmental Medicine , Lund University Hospital , Lund, Sweden;2. Department of Medicine , Skellefte? Hospital , Skellefte?, Sweden;3. Department of Medicine , Skellefte? Hospital , Skellefte?, Sweden;4. Department of Medicine and Public Health , Ume? University Hospital , Ume?, Sweden;5. Department of Public Health and Caring Sciences , Uppsala University , Uppsala, Sweden;6. Department of Public Health and Clinical Medicine , Ume? University , Ume?, Sweden |
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| 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. |
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| Keywords: | gene-environment interaction glutamyl-cysteine ligase glutathione S-transferases methylmercury plasma polyunsaturated fatty acids polymorphisms |
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