首页> 外文会议>Joint annual meeting of the International Society of Exposure Science and the International Society for Environmental Epidemiology >Maternal Blood Cadmium Concentrations and Whole Blood DNA Methylation during Pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI)
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Maternal Blood Cadmium Concentrations and Whole Blood DNA Methylation during Pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI)

机译:早期自闭症风险纵向调查(EARLI)中孕妇期间的孕妇血镉浓度和全血DNA甲基化

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Background: During pregnancy, the maternal epigenome may be responsive to environmental exposures. We tested whether maternal exposure to cadmium (Cd) results in differential maternal whole blood DNA methylation (DNAm) in early pregnancy. Methods: Maternal blood samples were collected at the initial study visit (during trimesters one or two of pregnancy) from 232 participants in the Early Autism Risk Longitudinal Investigation (EARLI) pregnancy cohort. We measured maternal blood Cd (n=215) using inductively coupled plasma mass spectrometry, which reflects recent exposure (blood t1/2 ~75 days), and measured maternal blood DNAm (n=201) on the Illumina 450K array; 93 non-smoking women had both measures available for analysis. Linear regression was used to test for site-specific associations between blood Cd and DNAm, adjusting for cell type composition and confounding variables. Results: The distribution of blood Cd was right skewed and log-transformed for statistical analyses. The geometric mean of blood Cd was 0.2 μg/L (Interquartile range = 0.13 μg/L). An interquartile range difference in blood Cd was associated with a 13.1% increase in B-cell proportions (95% CI: 1.0 - 25.2). In multivariable regression, six CpG sites were associated (p-value<10-5) with log blood Cd concentrations. At five of these sites, increasing blood Cd was associated with hypermethylation, and three corresponded to the genes LYN, TESC, and ESD. The CpG site near LYN was closest to genome-wide significance (p-value = 1.9x10-6), and an interquartile range difference in blood Cd was associated with an 8.4% increase in percent methylation at this site (95% CI: 5.1 -11.6). Conclusion: We report site-specific associations between DNAm and blood Cd in early pregnancy. Future work will consider the persistence of DNAm marks. Identified sites may be potential biomarkers of Cd exposure that can inform future epidemiological studies or implicate downstream gene pathways affected by Cd exposure.
机译:背景:在怀孕期间,母亲的表观基因组可能对环境暴露有反应。我们测试了孕早期母体是否接触镉(Cd)是否导致母体全血DNA甲基化(DNAm)差异。方法:在初次研究访视时(妊娠的一三个月或两个月),从早期自闭症风险纵向调查(EARLI)妊娠队列中的232名参与者中收集了母体血液样本。我们使用感应耦合等离子体质谱法测量了孕妇血液中的Cd(n = 215),它反映了最近的暴露时间(血液t1 / 2〜75天),并在Illumina 450K阵列上测量了孕妇血液DNAm(n = 201)。 93名非吸烟女性均可采用两种方法进行分析。使用线性回归测试血液Cd和DNAm之间的位点特异性关联,调整细胞类型组成和混淆变量。结果:血液中Cd的分布右偏并进行了对数转换以进行统计分析。血液中Cd的几何平均值为0.2μg/ L(四分位间距= 0.13μg/ L)。血液中Cd的四分位数间距差异与B细胞比例增加13.1%(95%CI:1.0-25.2)有关。在多变量回归中,六个CpG位点与对数血液Cd浓度相关(p值<10-5)。在这些部位中的五个处,血液中Cd的增加与甲基化过度有关,三个部位与LYN,TESC和ESD基因相对应。 LYN附近的CpG位点最接近全基因组意义(p值= 1.9x10-6),血液Cd的四分位数间距差异与该位点的甲基化百分比增加8.4%有关(95%CI:5.1) -11.6)。结论:我们报告了妊娠早期DNAm与血液Cd之间的特定部位关联。将来的工作将考虑DNAm标记的持久性。鉴定出的位点可能是潜在的镉暴露生物标志物,可以为将来的流行病学研究提供信息或暗示受镉暴露影响的下游基因途径。

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