rs1360780 of the FKBP5 gene modulates the association between maternal acceptance and regional gray matter volume in the thalamus in children and adolescents
rs1360780 of the FKBP5 gene modulates the association between maternal acceptance and regional gray matter volume in the thalamus in children and adolescents
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DOI：
10.1371/journal.pone.0221768
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发表时间：
2019-08
期刊：
影响因子：
3.7
通讯作者：
Izumi Matsudaira;K. Oba;H. Takeuchi;A. Sekiguchi;H. Tomita;Y. Taki;R. Kawashima
中科院分区：
文献类型：
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作者：
Izumi Matsudaira;K. Oba;H. Takeuchi;A. Sekiguchi;H. Tomita;Y. Taki;R. Kawashima
研究基因-环境相互作用(G×E)对大脑结构的影响可能有助于阐明与精神疾病风险相关的可能机制。Rs1360780(C/T)是编码FK506结合蛋白5(FKBP5)基因的功能性单核苷酸多态(SNP)，参与调节下丘脑-垂体-肾上腺(HPA)轴的应激反应。FKBP5的次要(T)等位基因被认为是应激相关疾病的危险等位基因，这是因为FKBP5的过度产生导致了应激信号与HPA轴的沟通障碍。以前的研究已经报道，儿童期虐待和rs1360780基因之间的相互作用会影响大脑皮质下区域的结构。然而，目前还不清楚这种SNP如何调节非不利环境和大脑结构之间的联系。在这项研究中，我们研究了在202名日本儿童中，rs1360780基因型和母亲接受度对区域灰质体积(RGMV)的交互作用。母亲的接受度是使用日本针对母亲的心理问卷进行评估的。基于体素形态计量的全脑多元回归分析显示，在T等位基因携带者中，母亲接受与左侧丘脑rGMV显著正相关，而在C/C纯合子中则显著负相关。事后分析显示，与C/C纯合子相比，T等位基因携带者的丘脑rGMV低于或低于母亲接受的70%。因此，我们的调查表明，母亲接受水平对大脑发育的影响因rs1360780基因而异。重要的是，我们发现T等位基因携带者和C/C纯合子之间的大脑结构差异处于母亲接受的低到中等水平，这并不等同于虐待。本研究通过强调调查非不利环境因素的作用的必要性，为G×E研究做出了贡献。
Investigating the effects of gene–environment interactions (G × E) with regard to brain structure may help to elucidate the putative mechanisms associated with psychiatric risk. rs1360780 (C/T) is a functional single-nucleotide polymorphism (SNP) in the gene encoding FK506–binding protein 5 (FKBP5), which is involved in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis stress responses. The minor (T) allele of FKBP5 is considered a risk allele for stress-related disorders, due to the overproduction of FKBP5, which results in impaired communication of stress signals with the HPA axis. Previous studies have reported that interactions between childhood maltreatment and the rs1360780 genotype affect structures in subcortical areas of the brain. However, it is unclear how this SNP modulates the association between non-adverse environments and brain structure. In this study, we examined the interactive effect of the rs1360780 genotype and maternal acceptance on the regional gray matter volume (rGMV) in 202 Japanese children. Maternal acceptance was assessed using a Japanese psychological questionnaire for mothers. Whole-brain multiple regression analysis using voxel-based morphometry showed a significant positive association between maternal acceptance and rGMV in the left thalamus of T-allele carriers, while a significant negative association was found in C/C homozygotes. Post-hoc analysis revealed that at or below the 70th percentiles of maternal acceptance, the T-allele carriers had a reduced thalamic rGMV compared with that of C/C homozygotes. Thus, our investigation indicated that the effect of the maternal acceptance level on brain development was different, depending on the rs1360780 genotype. Importantly, we found that the differences in brain structure between the T-allele carriers and C/C homozygotes at low to moderate levels of maternal acceptance, which is not equivalent to maltreatment. The present study contributes to the G × E research by highlighting the necessity to investigate the role of non-adverse environmental factors.