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

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)357-364
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume165
Issue number4
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

DNA Methylation
Genetic Promoter Regions
Methylation
Biomarkers
Depression
Brain-Derived Neurotrophic Factor
Brain
Genes
CpG Islands
Neuronal Plasticity
DNA
Saliva
Psychiatry
Exons
Neurons
Survival
Surveys and Questionnaires

Keywords

  • BDNF
  • Epigenetic
  • HumanMethylation 450K microarray
  • K6 score

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Altered DNA methylation status of human brain derived neurotrophis factor gene could be useful as biomarker of depression. / Song, Yixuan; Miyaki, Koichi; Suzuki, Tomoko; Sasaki, Yasuharu; Tsutsumi, Akizumi; Kawakami, Norito; Shimazu, Akihito; Takahashi, Masaya; Inoue, Akiomi; Kan, Chiemi; Kurioka, Sumiko; Shimbo, Takuro.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 165, No. 4, 01.01.2014, p. 357-364.

Research output: Contribution to journalArticle

Song, Y, Miyaki, K, Suzuki, T, Sasaki, Y, Tsutsumi, A, Kawakami, N, Shimazu, A, Takahashi, M, Inoue, A, Kan, C, Kurioka, S & Shimbo, T 2014, 'Altered DNA methylation status of human brain derived neurotrophis factor gene could be useful as biomarker of depression', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 165, no. 4, pp. 357-364. https://doi.org/10.1002/ajmg.b.32238
Song, Yixuan ; Miyaki, Koichi ; Suzuki, Tomoko ; Sasaki, Yasuharu ; Tsutsumi, Akizumi ; Kawakami, Norito ; Shimazu, Akihito ; Takahashi, Masaya ; Inoue, Akiomi ; Kan, Chiemi ; Kurioka, Sumiko ; Shimbo, Takuro. / Altered DNA methylation status of human brain derived neurotrophis factor gene could be useful as biomarker of depression. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2014 ; Vol. 165, No. 4. pp. 357-364.
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