PMID- 25505691 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20141216 LR - 20200930 IS - 2194-7511 (Print) IS - 2194-7511 (Electronic) IS - 2194-7511 (Linking) VI - 1 DP - 2013 TI - Quantitative leukocyte BDNF promoter methylation analysis in bipolar disorder. PG - 28 LID - 10.1186/2194-7511-1-28 [doi] LID - 28 AB - BACKGROUND: Bipolar disorder (BD) is a complex psychiatric phenotype with a high heritability and a multifactorial etiology. Multisite collaborative efforts using genome-wide association studies (GWAS) have identified only a portion of DNA sequence-based risk factors in BD. In addition to predisposing DNA sequence variants, epigenetic misregulation may play an etiological role in BD and account for monozygotic twin discordance, parental origin effects, and fluctuating course of BD. In this study, we investigated DNA methylation of the brain-derived neurotrophic factor (BDNF) gene in BD. METHODS: Fifty participants with BD were compared to the same number of age- and sex-matched controls for DNA methylation differences at BDNF promoters 3 and 5. DNA methylation reads were obtained using a mass spectrophotometer for 64 cytosine-guanine (CpG) sites in 36 CpG 'units' across three amplicons of BDNF promoters 3 and 5. RESULTS AND DISCUSSION: Methylation fractions differed between BD participants and controls for 11 of 36 CpG units. Five CpG units, mostly in promoter 5, remained significant after false discovery rate correction (FDR) (p values /= 0.61). Several of the significant CpGs overlapped with or were immediately adjacent to transcription factor binding sites (TFBSs) - including two of the FDR-significant CpG units in promoter 5. For the CpGs in promoter 3, there was a positive and significant correlation between age at sample collection and DNA methylation fraction (rho = 0.56, p = 2.8 x10(-5)) in BD cases, but not in controls. Statistically significant differences in mean methylation fraction at 5/36 CpG units (after FDR), some at or immediately adjacent to TFBSs, suggest possible relevance for the current findings to BD etiopathogenesis. The positive correlation between age and methylation seen in promoter 3 is consistent with age-related decline in BDNF expression previously reported. Future studies should provide more exhaustive epigenetic study of the BDNF locus to better characterize the relationship between BDNF methylation differences and BD. FAU - Strauss, John S AU - Strauss JS AD - Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M6J1H4 Canada. FAU - Khare, Tarang AU - Khare T AD - Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M6J1H4 Canada. FAU - De Luca, Vincenzo AU - De Luca V AD - Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M6J1H4 Canada. FAU - Jeremian, Richie AU - Jeremian R AD - Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M6J1H4 Canada. FAU - Kennedy, James L AU - Kennedy JL AD - Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M6J1H4 Canada. FAU - Vincent, John B AU - Vincent JB AD - Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M6J1H4 Canada. FAU - Petronis, Arturas AU - Petronis A AD - Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M6J1H4 Canada. LA - eng PT - Journal Article DEP - 20131230 PL - Germany TA - Int J Bipolar Disord JT - International journal of bipolar disorders JID - 101622983 PMC - PMC4215812 OTO - NOTNLM OT - Bipolar disorder OT - Epigenetic OT - Mass spectrometry OT - Methylation OT - Neurotrophin EDAT- 2013/01/01 00:00 MHDA- 2013/01/01 00:01 PMCR- 2013/12/30 CRDT- 2014/12/16 06:00 PHST- 2013/11/05 00:00 [received] PHST- 2013/12/09 00:00 [accepted] PHST- 2014/12/16 06:00 [entrez] PHST- 2013/01/01 00:00 [pubmed] PHST- 2013/01/01 00:01 [medline] PHST- 2013/12/30 00:00 [pmc-release] AID - 26 [pii] AID - 10.1186/2194-7511-1-28 [doi] PST - epublish SO - Int J Bipolar Disord. 2013 Dec 30;1:28. doi: 10.1186/2194-7511-1-28. eCollection 2013.