title: An investigation of modifying effects of metallothionein single-nucleotide polymorphisms on the association between mercury exposure and biomarker levels.
abstract: 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 methylmercury (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 (rs2270837) [corrected] AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or 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 MT1M TC and CC genotypes (n = 15), respectively.
  
  
  CONCLUSIONS
  Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general population.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan 48109-2029, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Goodrich
authors.forename: Brenda
authors.initials: B
authors.lastname: Gillespie
authors.forename: Robert
authors.initials: R
authors.lastname: Werner
authors.forename: Niladri
authors.initials: N
authors.lastname: Basu
authors.forename: Alfred
authors.initials: A
authors.lastname: Franzblau
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003723:Dental Amalgam / Q000633:toxicity; D003797:Dental Staff; D003815:Dentists; D004781:Environmental Exposure; D005260:Female; D005399:Fishes; D006197:Hair / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008297:Male; D008628:Mercury / Q000633:toxicity* / Q000652:urine; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000032:analysis / Q000633:toxicity*; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D015999:Multivariate Analysis; D016273:Occupational Exposure; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D008767:Methylmercury Compounds; D003723:Dental Amalgam; D008668:Metallothionein; D008628:Mercury