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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.