title: Altered DNA methylation status of human brain derived neurotrophis factor gene could be useful as biomarker of depression.
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 450 K 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.
authors.affiliation: Department of Clinical Research and Informatics, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Song
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Akizumi
authors.initials: A
authors.lastname: Tsutsumi
authors.forename: Norito
authors.initials: N
authors.lastname: Kawakami
authors.forename: Akihito
authors.initials: A
authors.lastname: Shimazu
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Akiomi
authors.initials: A
authors.lastname: Inoue
authors.forename: Chiemi
authors.initials: C
authors.lastname: Kan
authors.forename: Sumiko
authors.initials: S
authors.lastname: Kurioka
authors.forename: Takuro
authors.initials: T
authors.lastname: Shimbo
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D006801:Humans; D008019:Life Style; D008297:Male; D012959:Socioeconomic Factors; D013315:Stress, Psychological / Q000235:genetics
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor
keywords: BDNF; HumanMethylation 450K Microarray; K6 score; epigenetic