An Investigation of Modifying Effects of Metallothionein Single-Nucleotide Polymorphisms on the Association between Mercury Exposure and Biomarker Levels

• Published in: Environmental health perspectives Vol. 120; no. 4; pp. 530 - 534
• Main Authors: Wang, Yi, Goodrich, Jaclyn M., Gillespie, Brenda, Werner, Robert, Basu, Niladri, Franzblau, Alfred
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC National Institute of Environmental Health Sciences 01.04.2012; US Department of Health and Human Services
• Subjects: Adult; Aged; Animals; Bioaccumulation; Biological and medical sciences; Biological markers; Biomarkers - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Dental Amalgam - toxicity; Dental Staff; Dentists; Elemental mercury; Environment. Living conditions; Environmental Exposure; Environmental health; Environmental protection; Exposure; Female; Fish; Fishes; Genes; Genetic algorithms; Genetic aspects; Genotypes; Hair; Hair - chemistry; Hair - drug effects; Health aspects; Heterozygotes; Homozygotes; Humans; Intakes; Linear Models; Male; Medical sciences; Mercury; Mercury - toxicity; Mercury - urine; Metallothionein; Metallothionein - genetics; Metallothionein - metabolism; Metals and various inorganic compounds; Methylmercury; Methylmercury Compounds - analysis; Methylmercury Compounds - toxicity; Michigan - epidemiology; Middle Aged; Multivariate Analysis; Occupational Exposure; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Public health. Hygiene; Public health. Hygiene-occupational medicine; Regression; Regression analysis; Single nucleotide polymorphisms; Species Specificity; Surveys and Questionnaires; Toxicology; Urine; Michigan; United States; USA; gene-environment interaction; Biological marker; Exposure; biomarker; Heavy metal; Association; Health and environment; Genotype environment interaction; Nucleotide; single-nucleotide polymorphism; Mercury; Metallothionein; Polymorphism
• ISSN: 0091-6765; 1552-9924; 1552-9924
• DOI: 10.1289/ehp.1104079

Background: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. Objective: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure-biomarker relationships. Methods: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methyimercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. Results: The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the U.S. general population (0.95 μg/L and 0.47 μg/g, respectively). The mean estimated daily MeHg intake was 0.084 μg/kg/day (range, 0-0.98 μg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 μg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270836) AA genotype (n = 10) or the MT2A (rs 10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1Mot MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1MTC and CC genotypes (n = 15), respectively. Conclusion: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general population.