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 | Â | Â | Â | 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 |  |