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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

Plot of six Hg- and high-risk profile–associated EMID2 loci in 41 samples with Hg data by tertile. y-Axis represents EMID2 methylation β-value. Loci in order of appearance (+ strand, 5’ to 3’).
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f3: Plot of six Hg- and high-risk profile–associated EMID2 loci in 41 samples with Hg data by tertile. y-Axis represents EMID2 methylation β-value. Loci in order of appearance (+ strand, 5’ to 3’).

Mentions: Four of six loci are within 200 bases of EMID2’s transcription start site: cg13267931 is in the 5´ untranslated region upstream of the first exon, and cg14048874 in the gene body. Figure 3 illustrates their methylation by Hg tertile. In general, those infants in the highest tertile of exposure demonstrated the highest extent of methylation at each of the CpGs present on the array.


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)

Plot of six Hg- and high-risk profile–associated EMID2 loci in 41 samples with Hg data by tertile. y-Axis represents EMID2 methylation β-value. Loci in order of appearance (+ strand, 5’ to 3’).
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f3: Plot of six Hg- and high-risk profile–associated EMID2 loci in 41 samples with Hg data by tertile. y-Axis represents EMID2 methylation β-value. Loci in order of appearance (+ strand, 5’ to 3’).
Mentions: Four of six loci are within 200 bases of EMID2’s transcription start site: cg13267931 is in the 5´ untranslated region upstream of the first exon, and cg14048874 in the gene body. Figure 3 illustrates their methylation by Hg tertile. In general, those infants in the highest tertile of exposure demonstrated the highest extent of methylation at each of the CpGs present on the array.

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