Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Neurosci Res. 2013 Dec;77(4):208-14. doi: 10.1016/j.neures.2013.08.004. Epub 2013 Aug 22.
Accumulating evidence suggests that epigenetic alterations in brain-derived neurotrophic factor (BDNF) promoters are associated with the pathophysiology of psychiatric disorders. Epigenetic changes in BDNF were reported not only in brain tissues but also in other tissues, including peripheral blood cells (PBC) and saliva. We examined DNA methylation levels of BDNF promoters I and IV using genomic DNA derived from PBC of healthy controls (n=100), and patients with schizophrenia (n=100), all from the Japanese population, by pyrosequencing. The examined CpG sites were chosen based on previous epigenetic studies that reported altered DNA methylation. We found a significantly higher level of methylation at BDNF promoter I in patients with schizophrenia compared to controls, although the difference was small. Subsequent analysis revealed that in controls, the methylation level of BDNF promoters was associated with sex, and the methylation difference observed in promoter I was more prominent in male patients with schizophrenia. Epigenetic alteration of BDNF in the PBC might reflect the pathophysiology of schizophrenia, and could be a potential biomarker.
越来越多的证据表明，脑源性神经营养因子（BDNF）启动子中的表观遗传改变与精神疾病的病理生理学有关。BDNF 的表观遗传变化不仅在脑组织中，而且在其他组织中，包括外周血细胞（PBC）和唾液中都有报道。我们通过焦磷酸测序法，使用来自日本人群的健康对照者（n=100）和精神分裂症患者（n=100）的 PBC 中的基因组 DNA，检测了 BDNF 启动子 I 和 IV 的 DNA 甲基化水平。所检测的 CpG 位点是基于先前报道的 DNA 甲基化改变的表观遗传学研究选择的。我们发现精神分裂症患者的 BDNF 启动子 I 处的甲基化水平明显高于对照组，尽管差异很小。随后的分析表明，在对照组中，BDNF 启动子的甲基化水平与性别有关，在精神分裂症男性患者中观察到的启动子 I 中的甲基化差异更为明显。PBC 中 BDNF 的表观遗传改变可能反映了精神分裂症的病理生理学，并且可能是一个潜在的生物标志物。
