Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood.
Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood.
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DOI：
10.1038/s41598-017-00384-5
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发表时间：
2017-03-21
影响因子：
4.6
通讯作者：
Baccarelli AA
中科院分区：
文献类型：
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作者：
Cardenas A;Rifas-Shiman SL;Agha G;Hivert MF;Litonjua AA;DeMeo DL;Lin X;Amarasiriwardena CJ;Oken E;Gillman MW;Baccarelli AA
产前接触汞（一种已知的神经毒性金属）与儿童时期认知能力较低有关。胎儿表观遗传编程的破坏可以解释汞对神经发育的影响。我们在 321 份脐带血 DNA 样本中筛选了与母亲产前血液汞水平相关的表观基因组甲基化差异，并检查了这些改变在早期（n = 75；2.9-4.9 岁）和儿童中期（n = 291；6.7-10.5 岁）的持续性。在男性中，产前汞水平与局部脐带血 DNA 甲基化水平较低有关，该基因在儿童早期持续存在，并在儿童中期血液中减弱。 PON1 基因座的脐带血甲基化预示着儿童早期认知测试分数较低。 PON1 基因座的甲基化与一组独立的脐带血样本中的 PON1 表达相关。观察到的 PON1 基因的持续表观遗传破坏可能会调节人类的汞毒性，并可能作为暴露和疾病易感性的生物标志物。
Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury’s neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9–4.9 years) and mid-childhood (n = 291; 6.7–10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood. Cord blood methylation at the PON1 locus predicted lower cognitive test scores measured during early childhood. Methylation at the PON1 locus was associated with PON1 expression in an independent set of cord blood samples. The observed persistent epigenetic disruption of the PON1 gene may modulate mercury toxicity in humans and might serve as a biomarker of exposure and disease susceptibility.