title: Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals.
abstract: Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione S-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n=515), and total mercury content was measured. Average urine (1.06±1.24 microg/L) and hair mercury levels (0.49±0.63 microg/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption).
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Goodrich
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Brenda
authors.initials: B
authors.lastname: Gillespie
authors.forename: Robert
authors.initials: R
authors.lastname: Werner
authors.forename: Alfred
authors.initials: A
authors.lastname: Franzblau
authors.forename: Niladri
authors.initials: N
authors.lastname: Basu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D003797:Dental Staff; D003815:Dentists; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000652:urine; D005982:Glutathione Transferase / Q000235:genetics* / Q000652:urine; D006197:Hair / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D008297:Male; D008628:Mercury / Q000009:adverse effects* / Q000652:urine; D008767:Methylmercury Compounds / Q000009:adverse effects / Q000652:urine; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D051140:Selenoproteins / Q000235:genetics* / Q000652:urine
chemical_list: D015415:Biomarkers; D008767:Methylmercury Compounds; D051140:Selenoproteins; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D008628:Mercury