Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns
Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns
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DOI：
10.1093/ije/dyv032
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发表时间：
2015-08-01
影响因子：
7.7
通讯作者：
Fallin, M. Daniele
中科院分区：
文献类型：
--
作者：
Bakulski, Kelly M.;Lee, HwaJin;Fallin, M. Daniele
背景：人类暴露于广泛的环境污染物汞是癌症、心血管疾病和神经疾病等常见疾病的已知危险因素，其机制尚不明确。有证据表明，汞暴露可能会改变DNA甲基化水平，但到目前为止，还没有在全基因组范围内对早期生命的影响进行调查。方法：在美国马里兰州巴尔的摩招募了141名新生儿作为研究样本，并测定了脐带血样本中的总汞和甲基汞。我们使用基于阵列的方法Charm 2.0对全基因组DNA甲基化数据进行了量化，并使用区域查找分析来识别与浓度相关的差异甲基化区域(DMR)。结果：总汞浓度与ANGPT2内和PRPF18基因附近DMRS的甲基化有关[错误发现率(FDR)和0.05]，以及FOXD2和TCEANC2(FDR)附近的DMR甲基化
Background: Human exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated.Methods: A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Children's Study (NCS), we compared bisulfite-pyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures.Results: Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) < 0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR