Parental arsenic exposure and tissue-specific DNA methylation in Bangladeshi infants with spina bifida.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-10-19 DOI:10.1080/15592294.2024.2416345
Gwen Tindula, Sudipta Kumer Mukherjee, Sheikh Muhammad Ekramullah, D M Arman, Joynul Islam, Subrata Kumar Biswas, Benjamin C Warf, David C Christiani, Bernardo Lemos, Liming Liang, Andres Cardenas, Maitreyi Mazumdar
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引用次数: 0

Abstract

An emerging hypothesis linking arsenic toxicity involves altered epigenetic mechanisms, such as DNA methylation. In this study, we examined the relationship between parents' arsenic exposure and DNA methylation in tissues obtained from 28 infants with spina bifida from Bangladesh. We analyzed arsenic in parents' toenails using inductively coupled plasma mass spectrometry (ICP-MS). DNA methylation was measured in infants' dural tissue, buccal swabs, and whole blood using the Illumina Infinium MethylationEPIC BeadChip. We performed epigenome-wide association analyses (EWAS) and tested differentially methylated regions (DMRs). In EWAS, DNA methylation at cg24039697 in dural tissue was positively associated (β = 0.59, p = 7.6 × 10-9) with father's toenail arsenic concentrations, adjusting for covariates. We did not identify any CpG sites related to father's arsenic exposure in the other tissues, or any CpG sites related to mother's arsenic exposure. Gene ontology analysis identified many biological pathways of interest, including the Wnt signaling pathways. We identified several DMRs across the tissues related to arsenic exposure that included probes mapping to genes that have previously been identified in studies of neural tube defects. This study emphasizes the potential impact of arsenic exposure in fathers, often understudied in epidemiological studies, on DNA methylation in a unique neurological tissue specific to spina bifida.

孟加拉脊柱裂婴儿的父母砷暴露和组织特异性 DNA 甲基化。
一个新出现的与砷中毒有关的假说涉及到 DNA 甲基化等表观遗传机制的改变。在这项研究中,我们研究了父母的砷暴露与来自孟加拉国的 28 名脊柱裂婴儿组织中 DNA 甲基化之间的关系。我们使用电感耦合等离子体质谱法(ICP-MS)分析了父母脚趾甲中的砷含量。我们使用 Illumina Infinium MethylationEPIC BeadChip 对婴儿硬膜组织、口腔拭子和全血中的 DNA 甲基化进行了测量。我们进行了全表观基因组关联分析(EWAS),并检测了差异甲基化区域(DMR)。在 EWAS 中,硬脑膜组织中 cg24039697 处的 DNA 甲基化与父亲的趾甲砷浓度呈正相关(β = 0.59,p = 7.6 × 10-9),并调整了协变量。在其他组织中,我们没有发现任何与父亲砷暴露相关的 CpG 位点,也没有发现任何与母亲砷暴露相关的 CpG 位点。基因本体分析确定了许多相关的生物通路,包括 Wnt 信号通路。我们在各组织中发现了几个与砷暴露有关的 DMRs,其中包括以前在神经管缺陷研究中发现的基因的探针映射。这项研究强调了父亲的砷暴露对脊柱裂特有的神经组织中 DNA 甲基化的潜在影响,而流行病学研究往往对父亲的砷暴露研究不足。
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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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