The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight
The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight
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DOI：
10.1095/biolreprod.115.128066
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发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Marsit, Carmen J.
中科院分区：
文献类型：
--
作者：
Green, Benjamin B.;Armstrong, David A.;Marsit, Carmen J.
产妇压力与婴儿出生体重结果有关，而婴儿出生体重本身可能与以后的健康有关。胎盘充当胎儿环境的主要调节器，通过调节糖皮质激素的基因（包括11 β-羟类固醇脱氢酶（HPD 11 B）1型和2型基因）的活性来介导宫内应激，因此我们假设这些基因的变异将与婴儿出生体重相关。我们研究了这两个基因中六个位点的DNA甲基化水平，以及每个基因的mRNA表达，以及与婴儿出生体重的关系。校正潜在混杂因素的Logistic回归显示，在HSD 11B 1内单个CpG位点的甲基化与出生时大于胎龄之间存在显著相关性。此外，我们的分析确定了甲基化和基因表达之间的相关性，包括性别特异性的HSD 11B 2转录调控。我们的工作是第一个全面了解1型和2型HSD 11B胎盘中DNA甲基化和表达的观点之一，将表观遗传改变与胎儿应激和出生体重结果的调节联系起来。
Maternal stress has been linked to infant birth weight outcomes, which itself may be associated with health later in life. The placenta acts as a master regulator for the fetal environment, mediating intrauterine exposures to stress through the activity of genes regulating glucocorticoids, including the 11beta-hydroxysteroid dehydrogenase (HSD11B) type 1 and 2 genes, and so we hypothesized that variation in these genes will be associated with infant birth weight. We investigated DNA methylation levels at six sites across the two genes, as well as mRNA expression for each, and the relationship to infant birth weight. Logistic regressions correcting for potential confounding factors revealed a significant association between methylation at a single CpG site within HSD11B1 and being born large for gestational age. In addition, our analysis identified correlations between methylation and gene expression, including sex-specific transcriptional regulation of HSD11B2. Our work is one of the first comprehensive views of DNA methylation and expression in the placenta for both HSD11B types 1 and 2, linking epigenetic alterations with the regulation of fetal stress and birth weight outcomes.