产前黑碳暴露与脐带血中的 DNA 甲基化

IF 4.5 2区医学 Q1 INFECTIOUS DISEASES

International journal of hygiene and environmental health Pub Date : 2024-09-26 DOI:10.1016/j.ijheh.2024.114464

Chloe Friedman , Sierra Niemiec , Dana Dabelea , Katerina Kechris , Ivana V. Yang , John L. Adgate , Deborah H. Glueck , Sheena E. Martenies , Sheryl Magzamen , Anne P. Starling

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引用次数: 0

摘要

背景/目的产前暴露于环境空气污染与儿童期不良的心脏代谢结果有关。我们以前曾观察到，产前黑碳（BC）与儿童早期的脂肪细胞分泌的一种激素--脂肪连素成反比。方法在科罗拉多州健康起步研究中登记的 532 对母子中，我们对产前暴露于空气污染成分 BC 与脐带血中 DNA 甲基化之间的关系进行了一项全表观基因组关联研究。利用时空预测模型估算了母亲居住地的平均孕期环境 BC 值。DNA 甲基化使用 Illumina 450K 阵列进行测量。我们使用多元线性回归估计了产前环境 BC 与 429,246 个半胱氨酸-磷酸鸟嘌呤位点（CpGs）之间的关联，并对潜在的混杂因素进行了调整。我们使用 DMRff 和 ENmix-combp 确定了差异甲基化区域（DMRs）。在一部分参与者（n = 243）中，我们研究了 DNA 甲基化作为产前环境 BC 与儿童期较低的脂肪连蛋白之间关联的潜在中介因素的作用。据报道，注释到最高CpGs的几个基因具有免疫系统功能。通过 DMRff 和 ENmix-combp 发现了 24 个 DMRs。其中一个CpG（cg01123250）位于2号染色体，注释为UNC80基因，被发现介导了产前BC对儿童脂肪连素影响的约20%，但置信区间较宽（95% CI：3，84）。DNA甲基化可能部分介导了产前碱性磷酸酶与儿童心脏代谢结果之间的关系。

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Prenatal black carbon exposure and DNA methylation in umbilical cord blood

Background/objectives

Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts.

Methods

Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood.

Results

We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84).

Conclusions

Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes.

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来源期刊

International journal of hygiene and environmental health 医学-传染病学

CiteScore

11.50

自引率

5.00%

发文量

151

审稿时长

22 days

期刊介绍： The International Journal of Hygiene and Environmental Health serves as a multidisciplinary forum for original reports on exposure assessment and the reactions to and consequences of human exposure to the biological, chemical, and physical environment. Research reports, short communications, reviews, scientific comments, technical notes, and editorials will be peer-reviewed before acceptance for publication. Priority will be given to articles on epidemiological aspects of environmental toxicology, health risk assessments, susceptible (sub) populations, sanitation and clean water, human biomonitoring, environmental medicine, and public health aspects of exposure-related outcomes.