Table 2 Studies of lead exposure biomarkers and DNA methylation outcomes (4 studies available)
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 | Â | Â | 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 | Â | Â | Buffy coat | Average % methylation | Difference | Â | 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 |