Altered DNA methylation status of human brain derived neurotrophis factor gene could be useful as biomarker of depression

Yixuan Song, Koichi Miyaki, Tomoko Suzuki, Yasuharu Sasaki, Akizumi Tsutsumi, Norito Kawakami, Akihito Shimazu, Masaya Takahashi, Akiomi Inoue, Chiemi Kan, Sumiko Kurioka, Takuro Shimbo

研究成果: Article査読

50 被引用数 (Scopus)


Brain-derived neurotrophic factor (BDNF) is involved in the survival, development, and synaptic plasticity of neurons. BDNF is believed to be associated with the pathophysiology of psychiatric disorders. Several studies have suggested the relevance of DNA methylation in its promoter region with depression. Here, we report different methylation statuses in groups with different depressive scores or undergoing different levels of job-stress. DNA samples were extracted from the saliva of 774 Japanese workers, and the methylation status was determined using the Illumina HumanMethylation 450K Microarray. Depressive symptoms were measured using the Kessler's K6 questionnaire. Job-stress scales were assessed via a self-administered questionnaire. Independent DNA pools were formed based on K6 and job-strain scores, and the methylation levels were compared among these pools. The average DNA methylation rate was significantly decreased in the highest K6 score group compared to the lowest group (methylated signals, 14.2% vs. 16.5%, P=2·16×10-198). This difference remained for the CpG island in the promoter region (10.4% vs. 5.8%, P=3·67×10-133). Regarding the job-strain score, there was a slight increase in the methylation level of the whole gene in the group with the highest score compared to that with the lowest score; however, these groups showed no difference in the promoter region. Our results revealed significant changes in the DNA methylation status of the complete human BDNF gene in persons with depression compared to normal individuals, especially in the promoter region of exon 1. This indicates that DNA methylation in this gene is a promising biomarker for diagnosing depression.

ジャーナルAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
出版ステータスPublished - 2014 6月

ASJC Scopus subject areas

  • 遺伝学(臨床)
  • 精神医学および精神衛生
  • 細胞および分子神経科学


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