Influence of FKBP5 polymorphism and DNA methylation on structural changes of the brain in major depressive disorder.
Influence of FKBP5 polymorphism and DNA methylation on structural changes of the brain in major depressive disorder.
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DOI：
10.1038/srep42621
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发表时间：
2017-02-15
影响因子：
4.6
通讯作者：
Ham BJ
中科院分区：
文献类型：
--
作者：
Han KM;Won E;Sim Y;Kang J;Han C;Kim YK;Kim SH;Joe SH;Lee MS;Tae WS;Ham BJ
FKBP5基因rs1360780单核苷酸多态性与重性抑郁症（MDD）易感性相关我们研究了FKBP5 rs1360780等位基因变异、DNA甲基化和MDD诊断对整个大脑结构变化的相互作用。114例MDD患者和88例健康对照者接受了T1加权结构磁共振成像和FKBP5 rs1360780基因分型，包括内含子7的DNA甲基化。我们使用FreeSurfer分析了皮质和皮质下区域的体积以及皮质厚度。显著的基因型与诊断的相互作用被观察到的体积的左三角部，缘上回，上级顶叶小叶，右额缘，和后扣带回。T等位基因仅在MDD组中与这些脑区的显著体积减小相关，但右侧后扣带回中回除外。C等位基因纯合子组FKBP5基因甲基化与右侧额极横回厚度呈正相关。我们的研究结果表明，FKBP5基因及其表观遗传变化可能会影响参与情绪调节的几个脑区的形态学变化，这一过程可能与MDD的发展有关。
A single nucleotide polymorphism of rs1360780 in the FKBP5 gene is associated with a predisposition to developing major depressive disorder (MDD). We investigated the interactive effects of FKBP5 rs1360780 allelic variants, DNA methylation, and the diagnosis of MDD on structural changes of the entire brain. One hundred and fourteen patients with MDD and eighty-eight healthy controls underwent T1-weighted structural magnetic resonance imaging and FKBP5 rs1360780 genotyping, including DNA methylation of intron 7. We analyzed the volume of cortical and subcortical regions and cortical thickness using FreeSurfer. Significant genotype-by-diagnosis interactions were observed for volumes of the left pars triangularis, supramarginal gyrus, superior parietal lobule, right frontomarginal, and posterior midcingulate gyrus. The T allele was associated with significant volume reductions in these brain regions only in the MDD group except for the right posterior midcingulate gyrus. FKBP5 DNA methylation showed a positive correlation with the thickness of the right transverse frontopolar gyrus in the C allele homozygote group. Our findings suggest that the FKBP5 gene and its epigenetic changes could have influence on morphologic changes of several brain regions involved in emotion regulation, and that this process may be associated with the development of MDD.