Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.
Environ Health Perspect. 2013 Aug;121(8):971-7. doi: 10.1289/ehp.1205925. Epub 2013 Jun 11.
There is increasing epidemiologic evidence that arsenic exposure in utero, even at low levels found throughout much of the world, is associated with adverse reproductive outcomes and may contribute to long-term health effects. Animal models, in vitro studies, and human cancer data suggest that arsenic may induce epigenetic alterations, specifically by altering patterns of DNA methylation.
In this study we aimed to identify differences in DNA methylation in cord blood samples of infants with in utero, low-level arsenic exposure.
DNA methylation of cord-blood derived DNA from 134 infants involved in a prospective birth cohort in New Hampshire was profiled using the Illumina Infinium Methylation450K array. In utero arsenic exposure was estimated using maternal urine samples collected at 24-28 weeks gestation. We used a novel cell mixture deconvolution methodology for examining the association between inferred white blood cell mixtures in infant cord blood and in utero arsenic exposure; we also examined the association between methylation at individual CpG loci and arsenic exposure levels.
We found an association between urinary inorganic arsenic concentration and the estimated proportion of CD8+ T lymphocytes (1.18; 95% CI: 0.12, 2.23). Among the top 100 CpG loci with the lowest p-values based on their association with urinary arsenic levels, there was a statistically significant enrichment of these loci in CpG islands (p = 0.009). Of those in CpG islands (n = 44), most (75%) exhibited higher methylation levels in the highest exposed group compared with the lowest exposed group. Also, several CpG loci exhibited a linear dose-dependent relationship between methylation and arsenic exposure.
Our findings suggest that in utero exposure to low levels of arsenic may affect the epigenome. Long-term follow-up is planned to determine whether the observed changes are associated with health outcomes.
越来越多的流行病学证据表明，即使在世界大部分地区普遍存在的低水平环境砷暴露，也与不良生殖结局有关，并可能导致长期健康影响。动物模型、体外研究和人类癌症数据表明，砷可能通过改变 DNA 甲基化模式来诱导表观遗传改变。
本研究旨在识别宫内低水平砷暴露婴儿脐带血样本中的 DNA 甲基化差异。
使用 Illumina Infinium Methylation450K 阵列对新罕布什尔州前瞻性出生队列中 134 名婴儿的脐带血衍生 DNA 进行 DNA 甲基化分析。在妊娠 24-28 周时采集母亲尿液样本以估计宫内砷暴露。我们使用一种新的细胞混合物去卷积方法来研究婴儿脐带血中推断的白细胞混合物与宫内砷暴露之间的关系；我们还研究了单个 CpG 位点的甲基化与砷暴露水平之间的关系。
我们发现尿液无机砷浓度与估计的 CD8+T 淋巴细胞比例之间存在关联（1.18；95%CI：0.12，2.23）。在基于与尿砷水平的关联而具有最低 p 值的前 100 个 CpG 基因座中，这些基因座在 CpG 岛中存在统计学上显著的富集（p=0.009）。在 CpG 岛中（n=44），与最低暴露组相比，最高暴露组中大多数（75%）CpG 基因座的甲基化水平更高。此外，一些 CpG 基因座表现出甲基化与砷暴露之间的线性剂量依赖性关系。
我们的研究结果表明，宫内低水平砷暴露可能会影响表观基因组。计划进行长期随访以确定观察到的变化是否与健康结果相关。
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