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Table 3 Studies of mercury and other non-essential metals exposure biomarkers and DNA methylation outcomes (4 studies available)

From: Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence

First author, year Design Population Size Men (%) a Age Range (yr) a Exposure assessment Exposure categories DNA methylation Assessment DNA methylation endpoint Association 95% Confidence Interval or p-value Data pre-processing and adjustment factors
Mercury
Hanna, 2012 [29] CS U.S. (Study of Metals and Assisted Reproductive Technologies [SMART]) 43 0 Mean 36 (28 to 44) Whole blood by DRC-ICPMS Above and below the median Whole blood DNA     Normalization. QC reported. BEE NR. CH partially addressed. Data unadjusted. MCC NR.
         Site specific Illumina GoldenGate and bisulfite pyrosequencing of significant regionsb 1,505 CpG sites % methylation A trend towards hypermethylation if difference score > |30| (p < 0.05)   
       Median = 2.88 μg/L       
           GSTM1 39% increase p = 0.04  
           r pearson = 0.17 p = 0.27  
         Global by bisulfite pyrosequencing of LINE-1   ~0.2% decrease in median DNAm p = 0.42  
Goodrich, 2013 [85] CS US (Michigan Dental Association members) 131 49 55.8 ± 11.6 Total levels by direct Mercury Analyzer Per log-unit increase Buccal mucosa Average % methylation Difference   QC reported. Assessment of CH NR. Regression models adjusted for age and BMI.
         Quantitative pyrosequencing     
       Spot urine (Mean =0.7μg/L)   Site specific     
         DNMT1   −0.03 −0.32, 0.26  
         SEPW1   0.06 −0.12, 0.24  
         SEPP1   2.38 −1.23, 5.99  
         Global     
         LINE-1   0.37 −0.75, 1.49  
       Hair (Mean =0.37 μg/g)   Site specific     
         DNMT1   −0.13 −0.40, 0.14  
         SEPW1   −0.01 −0.19, 0.17  
         SEPP1   −2.02 −5.55, 1.51  
         Global     
         LINE-1   0.12 −0.96, 1.20  
Other non-essential metals
Tajuddin, 2013 [30] CS Spain (EPICURO study) 659 89 66 Nickel Per 1 μg/g increase Granulocyte DNA Average % methylation Difference   QC reported. CH addressed. Adjusted for age, sex, study region, and smoking status
       Toenail by ICPMS   Global by Quantitative pyrosequencing in LINE-1     
       (Median =0.47 μg/g)     0.02 0.03, 0.005  
Tellez-Plaza, 2014 [19] CS, CO 13 American Indian communities, US (SHS) 48 31.3 55 ± 7.3 Urine by ICPMS Above and below the median at baseline Global Methylamp Methylated DNA quantification kit (Epigentek) Logit-transformed % methylation relative to cytosine genomic content Odds ratio   QC reported. Models adjusted for age, sex, smoking status, BMI and, in prospective analyses only, log-transformed total count of white blood cells and percent of neutrophils.
       Antimony (Median = 0.27 μg/g)   Blood leukocytes in 1989–1991     
           1.24 0.71, 2.15  
       Tungsten (Median =0.13 μg/g)   Whole blood in 1997–1999   2.15 1.15, 4.01  
         Blood leukocytes in 1989–1991   1.46 0.85, 2.52  
         Whole blood in 1997–1999   0.93 0.46, 1.86  
  1. BEE: batch effects evaluation; BMI: body mass index; CDT, Comparative Toxicogenomics Database; CC: case-control; CH: Cell heterogeneity; CI: confidence interval; CO: cohort; CS: cross-sectional; NR: not reported LOD: limit of detection; QC: quality control.
  2. aSociodemographic data available in the article, not necessarily in the subsample without missing values in DNA methylation or exposures.
  3. bSignificance was defined as a difference score > |13| (p < 0.05) and >10% absolute difference between the means for each group.