Glucocorticoid receptor DNA methylation, childhood maltreatment and major depression.
Glucocorticoid receptor DNA methylation, childhood maltreatment and major depression.
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DOI：
10.1016/j.jad.2016.07.038
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发表时间：
2016-12
影响因子：
6.6
通讯作者：
Uddin M
中科院分区：
文献类型：
--
作者：
Bustamante AC;Aiello AE;Galea S;Ratanatharathorn A;Noronha C;Wildman DE;Uddin M
下丘脑-垂体-肾上腺（HPA）轴基因的DNA甲基化（DNAm）水平改变与儿童期虐待（CM）和抑郁症的暴露有关;然而，尚不清楚CM和抑郁症是否对糖皮质激素受体（NR 3C 1）DNAm具有联合和潜在的相互作用。我们调查了CM和终身重度抑郁症（MDD）对147名来自底特律社区健康研究的成年参与者的NR 3C 1 DNAm和基因表达（GE）的影响。使用全血来源的DNA通过焦磷酸测序评估NR 3C 1启动子区DNAm。定量RT-PCR测定来自白细胞来源的RNA的GE。线性回归模型用于检查CM、MDD和DNAm之间的关系。CM和MDD都是NR 3C 1 DNAm的显著预测因子：CM与EGR 1转录因子结合位点（TFBS）中DNAm的增加相关，而MDD与TFBS下游DNAm的减少相关。未观察到显著的CM-MDD相互作用。单独的CM与显著较低的NR 3C 1 GE相关。我们的CM报告是一个回顾性的自我报告的滥用，这可能会引入回忆偏倚。在全血中测量DNAm，可能不反映脑源性DNAm水平。CM和MDD均与NR 3C 1启动子区域中的DNAm水平改变相关，但是两种暴露之间的作用位置和方向不同，并且GE测量的功能效应似乎仅限于CM暴露。CM暴露可能在生物学上嵌入这个关键HPA轴基因。
Altered DNA methylation (DNAm) levels of hypothalamic-pituitary-adrenal (HPA) axis genes has been associated with exposure to childhood maltreatment (CM) and depression; however, it is unknown whether CM and depression have joint and potentially interacting effects on the glucocorticoid receptor (NR3C1) DNAm. We investigated the impact of CM and lifetime major depressive disorder (MDD) on NR3C1 DNAm and gene expression (GE) in 147 adult participants from the Detroit Neighborhood Health Study. NR3C1 promoter region DNAm was assessed via pyrosequencing using whole blood-derived DNA. Quantitative RT-PCR assays measured GE from leukocyte-derived RNA. Linear regression models were used to examine the relationship among CM, MDD, and DNAm. Both CM and MDD were significant predictors of NR3C1 DNAm: CM was associated with an increase in DNAm in an EGR1 transcription factor binding site (TFBS), whereas MDD was associated with a decrease in DNAm downstream of the TFBS. No significant CM-MDD interactions were observed. CM alone was associated with significantly lower NR3C1 GE. Our report of CM is a retrospective self-report of abuse, which may introduce recall bias. DNAm was measured in whole blood and may not reflect brain-derived DNAm levels. CM and MDD are both associated with altered DNAm levels in the NR3C1 promoter region, however the location and direction of effects differ between the two exposures, and the functional effects, as measured by GE, appear to be limited to CM exposure alone. CM exposure may be biologically embedded in this key HPA axis gene.
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人类血液和大脑衰老的一致性和不一致的DNA甲基化特征。
影响因子：
3.9
作者：
Farré P;Jones MJ;Meaney MJ;Emberly E;Turecki G;Kobor MS
通讯作者：
Kobor MS
影响因子：
4.8
作者：
Martin-Blanco, Ana;Ferrer, Marc;Carlos Pascual, Juan
通讯作者：
Carlos Pascual, Juan
影响因子：
3.7
作者：
Binder, E. B.;Kuenzel, H. E.;Holsboer, F.
通讯作者：
Holsboer, F.
DOI：
10.1097/00004583-199703000-00012
发表时间：
1997-03-01
影响因子：
13.3
作者：
Bernstein, DP;Ahluvalia, T;Handelsman, L
通讯作者：
Handelsman, L
影响因子：
3.7
作者：
Gola, Hannah;Engler, Andrea;Engler, Harald
通讯作者：
Engler, Harald