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Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes.

Maccani JZ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ - Environ. Health Perspect. (2015)

Bottom Line: Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS.Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile.Methylation at these loci was moderately correlated (correlation coefficients range, -0.33 to -0.45) with EMID2 expression.

View Article: PubMed Central - PubMed

Affiliation: Penn State Tobacco Center of Regulatory Science, Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA.

ABSTRACT

Background: Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly.

Objectives: We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes.

Methods: The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina's Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS) in an independent subset of 151 infants.

Results: We identified 339 loci with an average methylation difference > 0.125 between any two toenail Hg tertiles. Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS. Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were hypomethylated in the 16 high-risk profile infants' placentas. Methylation at these loci was moderately correlated (correlation coefficients range, -0.33 to -0.45) with EMID2 expression.

Conclusions: EMID2 hypomethylation may represent a novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral outcomes.

No MeSH data available.


Related in: MedlinePlus

Average β-value across six EMID2 loci associated with Hg and high-risk NNNS profile in an independent subset of 151 infants. Boxes extend from 25th to 75th percentile, horizontal bars represent medians, and whiskers extend 1.5 times the length of the interquartile range above and below the 75th and 25th percentiles, respectively. Outliers are represented as points.
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f4: Average β-value across six EMID2 loci associated with Hg and high-risk NNNS profile in an independent subset of 151 infants. Boxes extend from 25th to 75th percentile, horizontal bars represent medians, and whiskers extend 1.5 times the length of the interquartile range above and below the 75th and 25th percentiles, respectively. Outliers are represented as points.

Mentions: We then examined the average extent of methylation across all of the EMID2 loci in the NNNS subset, comparing those infants in the high-risk and non–high-risk groups. As shown in Figure 4, those in the high-risk group demonstrated hypomethylation of this gene. qRT-PCR in a subset of samples revealed moderate correlations between placental methylation at these loci and EMID2 gene expression, with correlation coefficients for individual CpG loci and expression ranging from –0.33 to –0.45 (see Supplemental Material, Figure S2).


Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes.

Maccani JZ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ - Environ. Health Perspect. (2015)

Average β-value across six EMID2 loci associated with Hg and high-risk NNNS profile in an independent subset of 151 infants. Boxes extend from 25th to 75th percentile, horizontal bars represent medians, and whiskers extend 1.5 times the length of the interquartile range above and below the 75th and 25th percentiles, respectively. Outliers are represented as points.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492267&req=5

f4: Average β-value across six EMID2 loci associated with Hg and high-risk NNNS profile in an independent subset of 151 infants. Boxes extend from 25th to 75th percentile, horizontal bars represent medians, and whiskers extend 1.5 times the length of the interquartile range above and below the 75th and 25th percentiles, respectively. Outliers are represented as points.
Mentions: We then examined the average extent of methylation across all of the EMID2 loci in the NNNS subset, comparing those infants in the high-risk and non–high-risk groups. As shown in Figure 4, those in the high-risk group demonstrated hypomethylation of this gene. qRT-PCR in a subset of samples revealed moderate correlations between placental methylation at these loci and EMID2 gene expression, with correlation coefficients for individual CpG loci and expression ranging from –0.33 to –0.45 (see Supplemental Material, Figure S2).

Bottom Line: Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS.Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile.Methylation at these loci was moderately correlated (correlation coefficients range, -0.33 to -0.45) with EMID2 expression.

View Article: PubMed Central - PubMed

Affiliation: Penn State Tobacco Center of Regulatory Science, Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA.

ABSTRACT

Background: Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly.

Objectives: We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes.

Methods: The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina's Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS) in an independent subset of 151 infants.

Results: We identified 339 loci with an average methylation difference > 0.125 between any two toenail Hg tertiles. Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS. Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were hypomethylated in the 16 high-risk profile infants' placentas. Methylation at these loci was moderately correlated (correlation coefficients range, -0.33 to -0.45) with EMID2 expression.

Conclusions: EMID2 hypomethylation may represent a novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral outcomes.

No MeSH data available.


Related in: MedlinePlus