title: Mercury biomarkers and DNA methylation among Michigan dental professionals.
abstract: Modification of the epigenome may be a mechanism underlying toxicity and disease following chemical exposure. Animal and human data suggest that mercury (Hg) impacts DNA methylation. We hypothesize that methylmercury and inorganic Hg exposures from fish consumption and dental amalgams, respectively, may be associated with altered DNA methylation at global repetitive elements (long interspersed elements, LINE-1) and candidate genes related to epigenetic processes (DNMT1) and protection against Hg toxicity (SEPW1, SEPP1). Dental professionals were recruited at Michigan Dental Association (MDA) meetings in 2009 and 2010. Subjects (n=131) provided survey data (e.g. exposure sources, demographics) and biological samples for Hg measurement and epigenetic analysis. Total Hg was quantified via atomic absorption spectrophotometry in hair and urine, indicative of methylmercury and inorganic Hg exposures, respectively. Global repetitive and candidate gene methylation was quantified via pyrosequencing of bisulfite converted DNA isolated from buccal mucosa. Hair Hg (geometric mean (95% CI): 0.37 (0.31-0.44) µg/g) and urine Hg (0.70 (0.60-0.83) µg/L) were associated with sources of exposure (fish consumption and dental amalgams, respectively). Multivariable linear regression revealed a trend of SEPP1 hypomethylation with increasing hair Hg levels, and this was significant (P<0.05) among males. The trend remained when excluding non-dentists. No significant relationships between urine Hg and DNA methylation were observed. Thus, in a limited cohort, we identified an association between methylmercury exposure and hypomethylation of a potentially labile region of the genome (SEPP1 promoter), and this relationship was gender specific.
authors: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. gaydojac@umich.edu
authors: Jaclyn M
authors: JM
authors: Goodrich
authors: Niladri
authors: N
authors: Basu
authors: Alfred
authors: A
authors: Franzblau
authors: Dana C
authors: DC
authors: Dolinoy
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000652:urine; D015331:Cohort Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D003723:Dental Amalgam / Q000009:adverse effects* / Q000737:chemistry; D003797:Dental Staff; D005247:Feeding Behavior; D005260:Female; D056726:Genetic Association Studies; D006197:Hair / Q000737:chemistry; D006801:Humans; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008628:Mercury / Q000009:adverse effects / Q000032:analysis* / Q000652:urine; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D015999:Multivariate Analysis; D016273:Occupational Exposure / Q000032:analysis*; D017747:Seafood; D051140:Selenoproteins / Q000235:genetics; D011795:Surveys and Questionnaires; D017132:Workplace / Q000592:standards
chemical_list: D015415:Biomarkers; D051140:Selenoproteins; D003723:Dental Amalgam; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D008628:Mercury