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Table 2 Studies of lead 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
Hanna, 2012 [29] CS U.S. (Study of Metals and Assisted Reproductive Technologies [SMART]) 24 0 Mean 36 (28 to 44) Blood by DRC-inductively coupled plasma mass spectrometry Above and below the median Whole blood DNA 1,505 CpG sites percent metylation    Normalization. QC reported. BEE NR. CH partially addressed. Data unadjusted. MCC NR.
Site specific Illumina GoldenGate and bisulfite pyrosequencing of significant regionsb A trend towards hypomethylation if difference score > |30| (P < 0.05)
Median = 0.73 μg/dL COL1A2
38% decrease in mean DNA m r = - 0.45; P = 0.004
P = 0.03
Global by bisulfite pyrosequencing of LINE-1 Approximately 0.1% increase in median DNAm P = 0.76
Tajuddin, 2013 [30] CS Spain (EPICURO study) 659 89 66 Toenail by ICPMS Per 1 μg/g increase Granulocyte DNA Average % methylation Difference   QC reported. CH addressed. Adjusted for age, sex, study region, and smoking status
(Median = 0.40 μg/g) Global by Quantitative pyrosequencing in LINE-1 −0.06 −0.1, 0.02
Li, 2013 [69] CS Wuxi region, China 110 91 mean = 39.45 (range 20-55) Blood by AAS   Peripheral leukocytes Average % methylation   P <0.001 No QC reported. CH addressed and adjustments not reported.
<100 μg/L Global LINE-1 by methylation-specific real-time PCR 86.3%,
100-200 μg/L 78.6%
>200 μg/L 73.9%
Wright, 2010 [68] CO US, Normative Aging Study 679 100 72.4    Buffy coat Average % methylation Difference   QC reported. Models adjusted for age, BMI, percent lymphocytes, education, smoking pack-years, and blood lead levels.
Global by quantitative pyrosequencing
Tibia Per IQR (15 μg/g) increase LINE-1 −0.07 −0.29, 0.14
Alu 0.02 −0.10, 0.13
Patella Per IQR (19 μg/g) increase LINE-1 −0.25 −0.44, –0.05
Alu −0.03 −0.14, 0.08
Blood Per IQR (2 g/dL) increase LINE-1 0.04 −0.10, 0.19
Alu 0.03 −0.05, 0.10
  1. AAS, atomic absorption spectrometry; BEE: batch effects evaluation; CH: Cell heterogeneity; DNAm, DNA methylation; IQR, interquartile range; LOD: limit of detection; MCC: multiple comparison correction; NR: not reported; 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.