Genetic Variation in Glutathione-Related Genes and Body Burden of Methylmercury

• Published in: Environmental health perspectives Vol. 116; no. 6; pp. 734 - 739
• Main Authors: Engström, Karin Schläwicke, Strömberg, Ulf, Lundh, Thomas, Johansson, Ingegerd, Vessby, Bengt, Hallmans, Göran, Skerfving, Staffan, Broberg, Karin
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences 01.06.2008
• Subjects: Adult; Animals; Arbetsmedicin och miljömedicin; Bioaccumulation; Blood plasma; Body burden; Chemical hazards; Environmental health; Environmental Health and Occupational Health; Erythrocytes - chemistry; Fatty acids; Fatty Acids, Unsaturated - blood; Fish; Fishes; Food Contamination - analysis; GCLC; GCLM; Gene Frequency; Genetic aspects; Genetic diversity; Genetic variation; Genotype; Genotypes; Glutamate-Cysteine Ligase - genetics; Glutamate-Cysteine Ligase - metabolism; Glutathione; Glutathione - chemistry; Glutathione - metabolism; Glutathione S-Transferase pi - genetics; Glutathione S-Transferase pi - metabolism; GSTP1; Health aspects; Health risk assessment; Health Sciences; Humans; Hälsovetenskap; Lead; Lean fishes; Medical and Health Sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Mercury; Metabolism; Methods; Methylmercury; Methylmercury Compounds - blood; Methylmercury Compounds - chemistry; Methylmercury Compounds - pharmacokinetics; Middle Aged; Multivariate Analysis; Occupational Health and Environmental Health; polymorphism; Polymorphism, Genetic; Polyunsaturated fatty acids; Risk assessment; Sweden; Water Pollutants, Chemical - blood; Water Pollutants, Chemical - chemistry; Water Pollutants, Chemical - pharmacokinetics; Sweden; methylmercury; GCLC; metabolism; polymorphism; GCLM; GSTP1
• ISSN: 0091-6765; 1552-9924; 1552-9924
• DOI: 10.1289/ehp.10804

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.