Differential DNA methylation in umbilical cord blood of infants exposed to mercury and arsenic in utero

Figures & data

Table 1. Selected maternal and infant characteristics and Hg and As concentrations

Characteristics
Mother-Infant Pairs (n)	138
Maternal age at delivery (years)	31 ± 4.6
Gestational age (weeks)	39.3 ± 1.39
Pre-pregnancy BMI (kg/m^2)	24.3 ± 4.2
Infant Birth weight (grams)	3415 ± 562
Infant Sex
Male	68 (49)
Female	70 (51)
Maternal Smoking During Pregnancy
No	115 (83)
Yes	7 (5)
Unknown	16 (12)
Maternal Race
White	135 (98)
Other	3 (2)
Education
Less than 11th grade	2 (2)
High school graduate or equivalent	13 (9)
Junior college graduate or some college	26 (19)
College graduate	52 (38)
Post-graduate education	28 (20)
Unknown	17 (12)
Exposure	Median (min-max)
Maternal Toenail Hg (μg/g)	0.07 (0.001–1.44)
^aMaternal Urinary Arsenic (μg/L)	3.19 (0.34–17.9)

^a Maternal Urinary Arsenic=As^III+As^V+MMA+DMA. Data are expressed as Mean ± SD or n (%), unless otherwise indicated.

Table 2. Estimated^a change in the proportion of leukocyte composition (95% CI) in cord blood in relationship to log₂ toenail Hg concentrations

	Overall Association		Stratified by Sex
			Males		Females
Cell type	% Change (95% CI)	P-value	% Change (95% CI)	P-value	% Change (95% CI)	P-value
CD8T	0.5 (−3.0, 4.0)	0.742	−3.5 (−11.0, 5.0)	0.414	1.4 (−2.0, 5.0)	0.395
CD4T	1.1 (−3.0, 6.0)	0.643	−6.6 (−18.0, 5.0)	0.274	2.3 (−3.0, 7.0)	0.367
NK cells	0.6 (−3.0, 5.0)	0.762	2.7 (−8.0, 1.3)	0.621	0.1 (−4.0, 5.0)	0.991
B-cells	2.3 (−1.0, 5.0)	0.116	−4.9 (−13.0, 3.0)	0.211	3.5 (1.0, 6.7)	0.027
Monocytes	−2.5 (−5.0, −1.0)	0.019	−1.9 (−8.0, 4.0)	0.508	−2.6 (−5.0, −1.0)	0.026
Granulocytes	−2.2 (−9.0, 5.0)	0.543	1.3 (−6.0, 3.3)	0.173	−5.0 (−1.3, 3.0)	0.196

^a Estimates from a multivariate linear regression model adjusted for infant sex and maternal age at delivery

Figure 1. Differentially methylated loci based on maternal toenail Hg. (A) Volcano plot for the relationship between log₂ toenail Hg on DNA methylation at all 348,569 CpGs analyzed. Red and blue lines indicate −log₁₀(1 × 10⁻⁴) and −log₁₀(0.05) P-values, respectively. Colors: Yellow=CpG island, Black=CpG Shore, Blue=Shelfs and Open sea. Symbols: Circle = Infinium Type II, Square = Infinium Type I (B) Location of the top 100-CpGs on the basis of P-values compared to all CpGs on the methylation array. Among the top 100 CpGs with lowest P-value, there was a significant enrichment in the N. Shore regions of CpG islands (P = 0.049).

Figure 2. Differentially methylated loci based on the interaction between maternal toenail Hg and urinary As. (A) Volcano plot for the relationship between the multiplicative interaction of log₂ toenail Hg and log₂ urinary As on DNA methylation at all 348,569 CpGs analyzed. Red and blue lines indicate −log₁₀(1 × 10⁻⁴) and −log₁₀(0.05) P-values, respectively. Colors: Yellow = CpG island, Black = CpG Shore, Blue=Shelfs and Open sea. Symbols: Circle = Infinium Type II, Square = Infinium Type I (B) Location of the top 100-CpGs on the basis of P-values compared to all CpGs on the methylation array. Among the top 100 CpGs with lowest P-value, there was a significant enrichment of CpG islands (P = 0.045) and S. Shore regions (P = 0.009).