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Table 4 Studies of persistent organic pollutants (POPs) and other endocrine disruptors biomarkers and DNA methylation outcomes (6 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

Chemical(s) (if PCBs, highest, lowest & median association and/or statistically significant)

Association

95% Confidence Interval or p-value

Adjustment Factors

Persistent Organic Pollutants

Rusiecki, 2008 [100]

CS

Greenland, Denmark (AMAP)

70

87

1967

Plasma by GC

Per log-transformed ng/g lipid increase

Peripheral leukocyte

Average % methylation

 

Difference

 

QC reported. BEE or CH assessment NR. Models adjusted for age and smoking,

PCB 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, p,p’-DDT, p,p’-DDE, β-HCH, Hexachlorobenzene, Chlordane, Cis-chlordane, Oxychlordane, α-Chlordane, Mirex, Toxaphene, ΣPCBs, ΣPOPs

Global by quantitative pyrosequencing in:

LINE-1

PCB 118

–0.73

P = 0.12

PCB 128

–0.01

P = 0.99

PCB 156, 170

–0.48

P = 0.26 and 0.15

Alu

 

PCB 156

–0.66

P < 0.01

PCB 52

–0.12

P = 0.36

PCB 99, 105

–0.51

P < 0.01 both

p,p’-DDT

–0.26

P = 0.01

p,p’-DDE

–0.38

P = 0.01

β-HCH

–0.48

<0.01

Oxychlordane

–0.32

<0.01

α-Chlordane

–0.75

P = 0.05

Mirex

–0.27

P = 0.01

ΣPCBs

–0.56

<0.01

ΣPOPs

–0.48

<0.01

Kim, 2010 [98]

CS

Uljin county, South Korea.

86

39.5

56.2 ± 7.0

Serum POPs by GC-HRMS

Per ng/g lipid increase

Whole blood.

Average % methylation

 

Pearson correlation

 

QC reported. BEE or CH assessment NR. Models adjusted for age, sex, BMI, cigarette smoking, and alcohol drinking

PCB 74, 99, 105, 118, 138, 146, 153, 156, 157, 164, 167, 172, 177, 178, 180, 183 and 187, β-HCH, HCB, Heptachlor epoxide, Oxychlordane, trans-Nonachlor, p,p’-DDE, p,p’-DDD, p,p’-DDT, Mirex, BDE47, BDE99

 

Global by quantitative pyrosequencing in:

 

LINE-1

 

PCB 157

–0.14

p ≥ 0.05

PCB 146

–0.02

p ≥ 0.05

PCB 105, 118, 156, 172, 180

–0.07

p ≥ 0.05

Alu

 

PCB 183

–0.23

p < 0.05

PCB 167

–0.05

p ≥ 0.05

PCB 177, 178

–0.14

p ≥ 0.05

Heptachlor epoxide,

–0.23

<0.05

Oxychlordane,

–0.28

<0.05

trans-nonachlordane,

–0.28

<0.05

p,p’-DDE,

–0.29

<0.01

p,p’-DDT,

–0.22

<0.05

BDE47

–0.25

<0.05

Lind, 2013 [99]

CS

Uppsala, Sweden (PIVUS study)

519

52

70

Serumby HRGC-HRMS

Per log-transformed ng/g lipid increase

Leukocytes

LUMA methylation indexb

 

Difference

 

QC NR. CH assessment NR. Same age. Models adjusted for sex and smoking status..

Global methylation by LUMA

PCB 74, 99, 105, 118, 126, 138, 153, 156, 157, 169, 170, 180, 189, 194, 206 and 209

Total PCB TEQ

−1.67

−3.17, −0.16

Non-ortho PCB TEQ

−1.76

−3.26, −0.26

Octachlorodibenzo-p-dioxin, HCB, TNC, p,p′-DDE, BDE47

Mono-ortho PCB TEQ

0.11

−1.37, 1.60

PCB 169

−3.27

−6.92, 0.37

PCB 206

−0.16

−3.71, 3.38

PCB 189

−0.56

−3.10, 1.97

Octachlorodibenzo-p-dioxin,

−3.19

−5.98, −0.39

p,p′-DDE

−2.87

−4.74, −1.00

Itoh, 2014 [20]

CS

Japan

399

0

53.9 ±10.2

Serum by GC-HRMS

Per increase in 1 quartile categories (as an ordinal variable)

Peripheral leukocytes

1 – (LUMA methylation indexb)

   

QC NR. CH assessment NR. Models adjusted for age, BMI, smoking status and alcohol drinking. Lipid-corrected values.

PCB 17, 28, 52/69, 48/47, 74, 66, 90/101, 99, 118, 114, 105, 146, 153, 164/163, 138, 128/162, 167, 156, 182/187, 183, 177, 180, 170, 189, 202, 198/199, 196, 203, 194, 208, 206 and 209, p,p’-DDE, o,p’-DDT, p,p’-DDT, trans-Nonachlor, cis-Nonachlor, Oxychlordane, β-HCH, HCB, Mirex

Global methylation by LUMA

PCB196

−0.009

−0.38, 0.36

PCB74

−0.64

−1.08, −0.20

PCB28 and 66

−0.23

−0.59, 0.12

PCB17

−0.43

−0.78, −0.08

PCB52/69

−0.33

−0.67, −0.0007

PCB114

−0.46

−0.88, −0.05

PCB183

−0.45

−0.82, −0.07

p,p’-DDE,

−0.77

−1.12, −0.42

o,p’-DDT,

−0.75

−1.11, −0.40

p,p’-DDT ,

−0.83

−1.17, −0.49

trans-Nonachlor,

−0.44

−0.84, −0.04

Oxychlordane,

−0.53

−0.90, −0.15

β-HCH,

−0.73

−0.79, −0.35

HCB,

−0.41

−0.79, −0.03

ΣPCBs

−0.19

−0.59, 0.20

Perfluorinated compounds

Watkins, 2014 [101]

CS

Mid-Ohio River Valley, US (C8 Health Project)

671

47

41.8 (20 to 80)

Blood by HPLC separation and detection by ITMS.

Per IQR increase in mean log ng/mL levels at 2 repeated visits 5 years apart

Peripheral leukocyte

  

Difference

 

QC and CH assessment NR. Models adjusted for age, gender, BMI, smoking and current drinker status

Global by quantitative pyrosequencing in LINE-1

Average % methylation

PFOA

106 ng/mL

−0.041

−0.098, 0.016

PFOS

12 ng/mL

0.204

0.090, 0.318

PFNA

0.8 ng/mL

0.064

−0.030, 0.158

PFHxS

2.6 ng/mL

0.020

−0.051, 0.091

Bisphenol A

Hanna, 2012 [29]

CS

U.S. (Study of Metals and Assisted Reproductive Technologies [SMART])

35

0

Mean 36 (28 to 44)

Serum

Above and below the median

Whole blood DNA

    

Normalization. QC reported. BEE NR. CH partially addressed. Data unadjusted. MCC NR.

Unconjugated BPA by HPLC

Median =2.39 μg/L

Site specific Illumina GoldenGate and bisulfite pyrosequencing of significant regionsb

1,505 CpG sites % methylation

A trend towards hypomethylation if difference score > |30| (p < 0.05)

 

TSP50

26% decrease in mean DNA m

P = 0.005

r pearson = -0.51

P = 0.001

Global by bisulfite pyrosequencing of LINE-1

~0.2% increase in median DNAm

P = 0.56

  1. CH: cell heterogeneity; BDE, polybrominated diphenyl ether; BEE: batch effect evaluation; BMI: body mass index; CDT, Comparative Toxicogenomics Database; CC: case-control; CI: confidence interval; CO: cohort; CS: cross-sectional; DNAm: DNA methylation; DDT, dichlorodiphenyl trichloroethane; DDE, dichlorodiphenyldichloroethylene; GC: gas chromatography; HPLC: high-performance liquid chromatography; HRGC-HRMS: high-resolution chromatography coupled to high-resolution mass spectometry; HRMS: high resolution mass spectrometry; IQR: interquartile range; ITMS: isotope-dilution tandem mass spectrometry; LOD: limit of detection; LUMA: Luminometric Methylation Assay; MCC: multiple comparisons correction; NR: not reported; PBDEs, polybrominated diphenyl ether; 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. b LUMA methylation index ranges from 1 (fully demethylated DNA) to 0 (fully methylated DNA).
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Clinical Epigenetics

ISSN: 1868-7083

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