美国新罕布什尔州出生队列研究中胎盘DNA甲基化的全表观基因组评估与砷暴露
Epigenome-Wide Assessment of DNA Methylation in the Placenta and Arsenic Exposure in the New Hampshire Birth Cohort Study (USA).
作者信息
Green Benjamin B, Karagas Margaret R, Punshon Tracy, Jackson Brian P, Robbins David J, Houseman E Andres, Marsit Carmen J
机构信息
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
出版信息
Environ Health Perspect. 2016 Aug;124(8):1253-60. doi: 10.1289/ehp.1510437. Epub 2016 Jan 15.
BACKGROUND
Arsenic is one of the most commonly encountered environmental toxicants, and research from model systems has suggested that one mode of its toxic activity may be through alterations in DNA methylation. In utero exposure to arsenic can affect fetal, newborn, and infant health, resulting in a range of phenotypic outcomes.
OBJECTIVES
This study examined variation in placental DNA methylation and its relationship to arsenic exposure in 343 individuals enrolled in the New Hampshire Birth Cohort Study.
METHODS
Linear regression models using a reference-free correction to account for cellular composition were employed to determine CpG loci affected by arsenic levels.
RESULTS
Total arsenic measured in maternal urine during the second trimester was not associated with methylation in the placenta, whereas arsenic levels quantified through maternal toenail collected at birth were associated with methylation at a single CpG locus (p = 4.1 × 10-8). Placenta arsenic levels were associated with 163 differentially methylated loci (false discovery rate < 0.05), with 11 probes within the LYRM2 gene reaching genome-wide significance (p < 10-8). Measurement of LYRM2 mRNA levels indicated that methylation was weakly to moderately correlated with expression (r = 0.15, p < 0.06). In addition, we identified pathways suggesting changes in placental cell subpopulation proportions associated with arsenic exposure.
CONCLUSIONS
These data demonstrate the potential for arsenic, even at levels commonly experienced in a U.S. population, to have effects on the DNA methylation status of specific genes in the placenta and thus supports a potentially novel mechanism for arsenic to affect long-term children's health.
CITATION
Green BB, Karagas MR, Punshon T, Jackson BP, Robbins DJ, Houseman EA, Marsit CJ. 2016. Epigenome-wide assessment of DNA methylation in the placenta and arsenic exposure in the New Hampshire Birth Cohort Study (USA). Environ Health Perspect 124:1253-1260; http://dx.doi.org/10.1289/ehp.1510437.
背景
砷是最常见的环境毒物之一，来自模型系统的研究表明，其毒性作用的一种方式可能是通过改变DNA甲基化。子宫内暴露于砷会影响胎儿、新生儿和婴儿的健康，导致一系列表型结果。
目的
本研究在新罕布什尔州出生队列研究的343名个体中，检测了胎盘DNA甲基化的变异及其与砷暴露的关系。
方法
采用使用无参考校正来考虑细胞组成的线性回归模型，以确定受砷水平影响的CpG位点。
结果
孕中期母体尿液中测得的总砷与胎盘中的甲基化无关，而出生时采集的母体趾甲中定量的砷水平与单个CpG位点的甲基化有关（p = 4.1×10-8）。胎盘砷水平与163个差异甲基化位点相关（错误发现率<0.05），LYRM2基因内的11个探针达到全基因组显著性（p < 10-8）。LYRM2 mRNA水平的测量表明，甲基化与表达呈弱至中度相关（r = 0.15，p < 0.06）。此外，我们确定了一些途径，表明与砷暴露相关的胎盘细胞亚群比例发生了变化。
结论
这些数据表明，即使在美国人群中常见的水平下，砷也有可能对胎盘中特定基因的DNA甲基化状态产生影响，从而支持了砷影响儿童长期健康的一种潜在新机制。
引用文献
Green BB, Karagas MR, Punshon T, Jackson BP, Robbins DJ, Houseman EA, Marsit CJ. 2016. Epigenome-wide assessment of DNA methylation in the placenta and arsenic exposure in the New Hampshire Birth Cohort Study (USA). Environ Health Perspect 124:1253-1260; http://dx.doi.org/10.1289/ehp.1510437.
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