Genetic variation in glutathione-related genes and body burden of methylmercury.
(2008) In Environmental Health Perspectives 116(6). p.734-739- Abstract
- BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit... (More)
- BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathione S-transferase pi 1 (GSTP1-105 and GSTP1-114)] genes on MeHg retention. METHODS: Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of fish (lean/fat fish two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake). RESULTS: The GSTP1 genotype modified Ery-Hg; effects were seen for GSTP1-105 and -114 separately, and combining them resulted in stronger effects. We found evidence of effect modification: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p = 0.038) compared with individuals with two or more variant alleles. The GCLM-588 genotype also influenced Ery-Hg (p = 0.035): Individuals with the GCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modification with increasing P-PUFA. CONCLUSIONS: These results suggest a role of GSH-related polymorphisms in MeHg metabolism. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1168758
- author
- Engström, Karin LU ; Strömberg, Ulf LU ; Lundh, Thomas LU ; Johansson, Ingegerd ; Vessby, Bengt ; Hallmans, Göran ; Skerfving, Staffan LU and Broberg Palmgren, Karin LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Environmental Health Perspectives
- volume
- 116
- issue
- 6
- pages
- 734 - 739
- publisher
- National Institute of Environmental Health Sciences
- external identifiers
-
- wos:000256254100025
- pmid:18560528
- scopus:46749087112
- ISSN
- 1552-9924
- DOI
- 10.1289/ehp.10804
- language
- English
- LU publication?
- yes
- id
- 53b16d33-0cf1-4a58-b92a-d2f5e538d387 (old id 1168758)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18560528?dopt=Abstract
- date added to LUP
- 2016-04-04 09:24:07
- date last changed
- 2022-02-28 07:47:10
@article{53b16d33-0cf1-4a58-b92a-d2f5e538d387, abstract = {{BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathione S-transferase pi 1 (GSTP1-105 and GSTP1-114)] genes on MeHg retention. METHODS: Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of fish (lean/fat fish two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake). RESULTS: The GSTP1 genotype modified Ery-Hg; effects were seen for GSTP1-105 and -114 separately, and combining them resulted in stronger effects. We found evidence of effect modification: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p = 0.038) compared with individuals with two or more variant alleles. The GCLM-588 genotype also influenced Ery-Hg (p = 0.035): Individuals with the GCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modification with increasing P-PUFA. CONCLUSIONS: These results suggest a role of GSH-related polymorphisms in MeHg metabolism.}}, author = {{Engström, Karin and Strömberg, Ulf and Lundh, Thomas and Johansson, Ingegerd and Vessby, Bengt and Hallmans, Göran and Skerfving, Staffan and Broberg Palmgren, Karin}}, issn = {{1552-9924}}, language = {{eng}}, number = {{6}}, pages = {{734--739}}, publisher = {{National Institute of Environmental Health Sciences}}, series = {{Environmental Health Perspectives}}, title = {{Genetic variation in glutathione-related genes and body burden of methylmercury.}}, url = {{http://dx.doi.org/10.1289/ehp.10804}}, doi = {{10.1289/ehp.10804}}, volume = {{116}}, year = {{2008}}, }