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新生儿的产前暴露与DNA甲基化:南非德班的一项试点研究。

Prenatal exposures and DNA methylation in newborns: a pilot study in Durban, South Africa.

作者信息

Goodrich Jaclyn M, Reddy Poovendhree, Naidoo Rajen N, Asharam Kareshma, Batterman Stuart, Dolinoy Dana C

机构信息

Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA.

Department of Community Health Studies, Durban University of Technology, Durban, South Africa.

出版信息

Environ Sci Process Impacts. 2016 Jul 13;18(7):908-17. doi: 10.1039/c6em00074f.

Abstract

The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive. Families living in a high air pollution region (south Durban, n = 11) and a low air pollution region (north Durban, n = 11) with comparable socioeconomic characteristics were selected for analysis. DNA methylation was quantified in cord blood plasma DNA at >430 000 CpG sites using the Infinium HumanMethylation450 BeadChip. Sites associated with living in south Durban or maternal HIV infection (p < 0.001) were more likely to be hypomethylated and located in CpG islands. Top differentially methylated sites by region of Durban were enriched in pathways related to xenobiotic metabolism, oxygen and gas transport, and sensory perception of chemical stimuli when performing gene set enrichment testing with LRpath. Differentially methylated sites by maternal HIV status were enriched in cytochrome P450s, pathways involved in detection of chemical stimuli, metabolic processes, and viral regulation and processing. Given the small sample size of the study, future work examining the impact of prenatal exposures to air pollution, maternal infection, and antiviral treatment on the epigenome and downstream health implications is merited in Sub-Saharan African populations.

摘要

子宫内环境有可能影响表观遗传编程,进而影响后代健康。尽管生活在非洲城市的孕妇接触多种可能影响其发育中胎儿的化学物质和感染源,但这些地区尚未对新生儿表观基因组进行研究。我们使用母婴环境(MACE)出生队列的一个试点样本,评估产前接触空气污染和母体人类免疫缺陷病毒(HIV)是否与整个表观基因组的DNA甲基化变化相关,其中36%的母亲为HIV阳性。选择生活在具有可比社会经济特征的高空气污染地区(德班南部,n = 11)和低空气污染地区(德班北部,n = 11)的家庭进行分析。使用Infinium HumanMethylation450 BeadChip在超过43万个CpG位点对脐带血血浆DNA中的DNA甲基化进行定量。与生活在德班南部或母体HIV感染相关的位点(p < 0.001)更可能发生低甲基化,且位于CpG岛中。在用LRpath进行基因集富集测试时,按德班地区划分的顶级差异甲基化位点在与异源生物代谢、氧气和气体运输以及化学刺激的感官感知相关的途径中富集。按母体HIV状态划分的差异甲基化位点在细胞色素P450、参与化学刺激检测的途径、代谢过程以及病毒调节和加工中富集。鉴于该研究样本量较小,未来在撒哈拉以南非洲人群中研究产前接触空气污染、母体感染和抗病毒治疗对表观基因组及下游健康影响的工作是有必要的。

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