Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes
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DOI：
10.1017/s0954579414001357
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发表时间：
2015-02-01
影响因子：
3.3
通讯作者：
Holbrook, Joanna D.
中科院分区：
文献类型：
--
作者：
Chen, Li;Pan, Hong;Holbrook, Joanna D.
早期生活环境与基因型相互作用决定稳定的表型结果。在这里，我们研究了脑源性神经营养因子（BDNF）基因（Val66Met）变异的影响，该基因是整个中枢神经系统突触可塑性的基础，在产前母亲焦虑与新生儿DNA甲基化相关的程度上。我们还研究了新生儿DNA甲基化与脑亚结构体积之间的关系，作为BDNF基因型的功能。婴儿BDNF基因型显著影响产前焦虑对出生时表观基因组的关联，以及表观基因组与新生儿大脑结构之间的关联。与Met/valine （Val）和Val/Val基因型相比，产前母亲焦虑对蛋氨酸(Met)/Met基因型婴儿DNA甲基化的影响更大。与Met/Val和Val/Val携带者相比，Met/Met携带者中甲基化水平与右杏仁核体积共变的胞嘧啶-磷酸-鸟嘌呤位点显著增加。相比之下，与Met/Val或Met/Met基因型的婴儿相比，Val/Val婴儿的胞嘧啶-磷酸-鸟嘌呤位点与左海马体积共变较多。因此，产前母体焦虑与BDNF Val66Met多态性在表观基因组水平上的相互作用在杏仁核和海马结构中有不同的反映。这些发现表明，BDNF基因型调节了甲基组对早期环境的敏感性，对特定环境条件的差异敏感性可能是组织和功能特异性的。
Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine-phosphate-guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine-phosphate-guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety x BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.