出生时的 DNA 甲基化可能会介导产前铅(Pb)暴露与婴儿神经发育结果之间的关系。

IF 4.8 Q1 GENETICS & HEREDITY Environmental Epigenetics Pub Date : 2021-06-16 eCollection Date: 2021-01-01 DOI:10.1093/eep/dvab005
Christine A Rygiel, Dana C Dolinoy, Kelly M Bakulski, Max T Aung, Wei Perng, Tamara R Jones, Maritsa Solano-González, Howard Hu, Martha M Tellez-Rojo, Lourdes Schnaas, Erika Marcela, Karen E Peterson, Jaclyn M Goodrich
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引用次数: 0

摘要

早年的铅(Pb)暴露与不良的神经发育结果有关。最近的证据表明,DNA 甲基化(DNAm)在认知中起着关键作用,而铅暴露也被证明会改变 DNAm。然而,DNAm是否是铅神经毒性机制的一部分尚不清楚。这项纵向研究调查了墨西哥早期环境毒物暴露(ELEMENT)研究中 85 对母婴的特定孕期(T1、T2 和 T3)母体血液中铅浓度、脐带血中基因特异性 DNAm 与婴儿 12 个月和 24 个月大时神经发育结果(智力发育指数、精神运动发育指数以及定向/参与和情绪调节行为评分量表)之间的关系。在这项试点研究的中介分析中,P CCSER1(探针 ID cg02901723)中介了 T2 Pb 对 24 个月定向/参与的影响[间接效应估计值 4.44,95% 置信区间 (-0.09, 10.68),P = 0.06]和情绪调节[3.62 (-0.05, 8.69),P = 0.05]。Cg18515027(GCNT1)DNAm介导了T1 Pb [-4.94 (-10.6, -0.77),P = 0.01]和T2 Pb [-3.52 (-8.09, -0.36),P = 0.02]与24个月EMOCI的关联,但T2 Pb与24个月精神运动发育指数之间存在正的间接效应估计值[1.25 (-0.11, 3.32),P = 0.09]。cg19703494(TRAPPC6A)DNAm的间接效应在T2 Pb与24个月精神发育指数之间具有显著性[1.54(0,3.87),P = 0.05]。cg23280166 (VPS11) DNAm 对 T3 Pb 和 24 个月智力发育指数也有间接影响 [2.43 (-0.16, 6.38),P = 0.08]。这些关联提供了基因特异性 DNAm 作为产前铅与后代不良认知结果之间中介的初步证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes.

Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, P < 0.1 was considered significant. DNAm at a locus in CCSER1 (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), P = 0.06] and emotional regulation [3.62 (-0.05, 8.69), P = 0.05]. Cg18515027 (GCNT1) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), P = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), P = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), P = 0.09]. The indirect effect was significant for cg19703494 (TRAPPC6A) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), P = 0.05]. There was also an indirect effect of cg23280166 (VPS11) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), P = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.

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来源期刊
Environmental Epigenetics
Environmental Epigenetics GENETICS & HEREDITY-
CiteScore
6.50
自引率
5.30%
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0
审稿时长
17 weeks
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