Ihara Kazushige, Fuchikami Manabu, Hashizume Masahiro, Okada Satoshi, Kawai Hisashi, Obuchi Shuichi, Hirano Hirohiko, Fujiwara Yoshinori, Hachisu Mitsugu, Hongyong Kim, Morinobu Shigeru
Hirosaki University Graduate School of Medicine, Department of Social Medicine, Aomori, Japan.
Toho University Faculty of Medicine, Department of Psychosomatic Medicine, Tokyo, Japan.
Int J Geriatr Psychiatry. 2018 Oct;33(10):1312-1318. doi: 10.1002/gps.4927. Epub 2018 Jun 28.
Brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of psychiatric disorders in adults and elderly individuals, and as a result, the DNA methylation (DNAm) of the BDNF gene in peripheral tissues including blood has been extensively examined to develop a useful biomarker for psychiatric disorders. However, studies to date have not previously investigated the effect of age on DNAm of the BDNF gene in blood. In this context, we measured DNAm of 39 CpG units in the CpG island at the promoter of exon I of the BDNF gene.
We analyzed genomic DNA from peripheral blood of 105 health Japanese women 20 to 80 years of age to identify aging-associated change in DNAm of the BDNF gene. In addition, we examined the relationship between total MMSE scores, numbers of stressful life events, and serum BDNF levels on DNAm of the BDNF gene. The DNAm rate at each CpG unit was measured using a MassArray system (Agena Bioscience), and serum BDNF levels were measured by ELISA.
There was a significant correlation between DNAm and age in 13 CpGs. However, there was no significant correlation between DNAm and total MMSE scores, numbers of life events, or serum BDNF levels.
Despite the small number of subjects and the inclusion of only female subjects, our results suggest that DNAm of 13 CpGs of the BDNF gene may be an appropriate biomarker for aging and useful for predicting increased susceptibility to age-related psychiatric disorders.
脑源性神经营养因子（BDNF）参与成人和老年人精神疾病的病理生理过程，因此，包括血液在内的外周组织中BDNF基因的DNA甲基化（DNAm）已被广泛研究，以开发一种用于精神疾病的有用生物标志物。然而，迄今为止的研究尚未调查年龄对血液中BDNF基因DNAm的影响。在此背景下，我们测量了BDNF基因外显子I启动子区域CpG岛中39个CpG位点的DNAm。
我们分析了105名年龄在20至80岁之间的健康日本女性外周血中的基因组DNA，以确定BDNF基因DNAm与衰老相关的变化。此外，我们还研究了简易精神状态检查表（MMSE）总分、应激性生活事件数量和血清BDNF水平与BDNF基因DNAm之间的关系。使用MassArray系统（Agena Bioscience）测量每个CpG位点的DNAm率，并通过酶联免疫吸附测定法（ELISA）测量血清BDNF水平。
13个CpG位点的DNAm与年龄之间存在显著相关性。然而，DNAm与MMSE总分、生活事件数量或血清BDNF水平之间没有显著相关性。
尽管样本量较小且仅纳入了女性受试者，但我们的结果表明，BDNF基因13个CpG位点的DNAm可能是衰老的合适生物标志物，有助于预测与年龄相关的精神疾病易感性增加。
