Differential DNA methylation in umbilical cord blood of infants exposed to mercury and arsenic in utero
Differential DNA methylation in umbilical cord blood of infants exposed to mercury and arsenic in utero
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DOI：
10.1080/15592294.2015.1046026
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发表时间：
2015-06-03
期刊：
影响因子：
3.7
通讯作者：
Marsit, Carmen J.
中科院分区：
文献类型：
--
作者：
Cardenas, Andres;Koestler, Devin C.;Marsit, Carmen J.
汞和砷是已知的发育毒性物质。产前暴露与不良的儿童健康结果有关，这可能部分是由表观遗传改变介导的，表观遗传改变也可能导致免疫谱的改变。在这项研究中，我们检查了产前汞暴露对脐带血DNA甲基化和白细胞组成的关系，并评估了产前砷暴露与DNA甲基化和脐带血白细胞组成的相互作用。使用Illumina Infinium Methylation450阵列对138对母婴进行产后足趾汞、产前尿砷浓度和新生儿脐带血检测。白细胞组成是通过DNA甲基化测量推断出来的。趾甲汞浓度加倍与估计单核细胞比例下降2.5%相关（95% CI: 5.0%, 1.0%）。仅在女性中观察到b细胞比例增加3.5% （95% CI: 1.0, 7.0）。在与趾甲汞含量相关的前100个CpG中（按P值排序），位于CpG岛北岸地区的位点显著富集（P = 0.049），其中大部分位点（85%）被超甲基化。在砷与汞相互作用的前100个CpG位点中，位于CpG岛（P = 0.045）和南岸地区（P = 0.009）的位点比例高于预期，并且所有这些位点都是高甲基化的。这项工作支持了汞可能导致表观遗传变异和免疫细胞比例变化的假设，并表明在子宫内接触汞和砷，即使是低水平，也可能相互作用，影响表观基因组。
Mercury and arsenic are known developmental toxicants. Prenatal exposures are associated with adverse childhood health outcomes that could be in part mediated by epigenetic alterations that may also contribute to altered immune profiles. In this study, we examined the association between prenatal mercury exposure on both DNA methylation and white blood cell composition of cord blood, and evaluated the interaction with prenatal arsenic exposure. A total of 138 mother-infant pairs with postpartum maternal toenail mercury, prenatal urinary arsenic concentrations, and newborn cord blood were assessed using the Illumina Infinium Methylation450 array. White blood cell composition was inferred from DNA methylation measurements. A doubling in toenail mercury concentration was associated with a 2.5% decrease (95% CI: 5.0%, 1.0%) in the estimated monocyte proportion. An increase of 3.5% (95% CI: 1.0, 7.0) in B-cell proportion was observed for females only. Among the top 100 CpGs associated with toenail mercury levels (ranked on P-value), there was a significant enrichment of loci located in North shore regions of CpG islands (P = 0.049), and the majority of these loci were hypermethylated (85%). Among the top 100 CpGs for the interaction between arsenic and mercury, there was a greater than expected proportion of loci located in CpG islands (P = 0.045) and in South shore regions (P = 0.009) and all of these loci were hypermethylated. This work supports the hypothesis that mercury may be contributing to epigenetic variability and immune cell proportion changes, and suggests that in utero exposure to mercury and arsenic, even at low levels, may interact to impact the epigenome.