Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study.
Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study.
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在一项前瞻性自闭症研究中，胎盘 DNA CYP2E1 和 IRS2 甲基化水平与儿童结局相关。
DOI：
10.1093/hmg/ddz084
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发表时间：
2019
影响因子：
3.5
通讯作者：
LaSalle,JanineM
中科院分区：
文献类型：
--
作者：
Zhu,Yihui;Mordaunt,CharlesE;Yasui,DagH;Marathe,Ria;Coulson,RochelleL;Dunaway,KeithW;Jianu,JuliaM;Walker,CherylK;Ozonoff,Sally;Hertz-Picciotto,Irva;Schmidt,RebeccaJ;LaSalle,JanineM
DNA甲基化作用于与自闭症谱系障碍（ASD）相关的遗传和环境因素的界面。胎盘通常在出生时被丢弃，是预测儿童ASD的DNA甲基化模式的潜在丰富来源。在这里，我们对高危妊娠的前瞻性研究MARBLES（婴儿自闭症风险标志物-学习早期迹象）的胎盘进行了全甲基组分析。与正常发育的对照组相比，共有400个差异甲基化区域（DMRs）区分了储存于后来诊断为ASD的儿童的胎盘。这些ASD DMRs在启动子上显著富集，映射到596个在神经元发育中功能富集的基因，并且重叠遗传ASD风险。ASD DMRs cyp2e1anddirs2达到全基因组意义，通过焦磷酸测序复制，并与脑中的表达差异相关。cyp2e1甲基化与DMR内ASD诊断和基因型相关。相反，atirs2的甲基化不受DMR基因型的影响，但受孕前母体产前维生素使用的影响。因此，本研究确定了胎盘中ASD的两个潜在有用的早期表观遗传标记。
DNA methylation acts at the interface of genetic and environmental factors relevant for autism spectrum disorder (ASD). Placenta, normally discarded at birth, is a potentially rich source of DNA methylation patterns predictive of ASD in the child. Here, we performed whole methylome analyses of placentas from a prospective study MARBLES (Markers of Autism Risk in Babies—Learning Early Signs) of high-risk pregnancies. A total of 400 differentially methylated regions (DMRs) discriminated placentas stored from children later diagnosed with ASD compared to typically developing controls. These ASD DMRs were significantly enriched at promoters, mapped to 596 genes functionally enriched in neuronal development, and overlapped genetic ASD risk. ASD DMRs atCYP2E1andIRS2reached genome-wide significance, replicated by pyrosequencing and correlated with expression differences in brain. Methylation atCYP2E1associated with both ASD diagnosis and genotype within the DMR. In contrast, methylation atIRS2was unaffected by within DMR genotype but modified by preconceptional maternal prenatal vitamin use. This study therefore identified two potentially useful early epigenetic markers for ASD in placenta.