PMID- 28785205
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 11
DP  - 2017
TI  - Differential SLC1A2 Promoter Methylation in Bipolar Disorder With or Without 
      Addiction.
PG  - 217
LID - 10.3389/fncel.2017.00217 [doi]
LID - 217
AB  - While downregulation of excitatory amino acid transporter 2 (EAAT2), the main 
      transporter removing glutamate from the synapse, has been recognized in bipolar 
      disorder (BD), the underlying mechanisms of downregulation have not been 
      elucidated. BD is influenced by environmental factors, which may, via epigenetic 
      modulation of gene expression, differentially affect illness presentation. This 
      study thus focused on epigenetic DNA methylation regulation of SLC1A2, encoding 
      for EAAT2, in BD with variable environmental influences of addiction. High 
      resolution melting PCR (HRM-PCR) and thymine-adenine (TA) cloning with sequence 
      analysis were conducted to examine methylation of the promoter region of the 
      SLC1A2. DNA was isolated from blood samples drawn from BD patients (N = 150) with 
      or without addiction to alcohol, nicotine, or food, defined as binge eating, and 
      matched controls (N = 32). In comparison to controls, the SLC1A2 promoter region 
      was hypermethylated in BD without addiction but was hypomethylated in BD with 
      addiction. After adjusting for age and sex, the association of methylation levels 
      with nicotine addiction (p = 0.0009) and binge eating (p = 0.0002) remained 
      significant. Consistent with HRM-PCR, direct sequencing revealed increased 
      methylation in CpG site 6 in BD, but decreased methylation in three CpG sites (6, 
      48, 156) in BD with alcohol and nicotine addictions. These results suggest that 
      individual point methylation within the SLC1A2 promoter region may be modified by 
      exogenous addiction and may have a potential for developing clinically valuable 
      epigenetic biomarkers for BD diagnosis and monitoring.
FAU - Jia, Yun-Fang
AU  - Jia YF
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      RochesterMN, United States.
FAU - Choi, YuBin
AU  - Choi Y
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      RochesterMN, United States.
FAU - Ayers-Ringler, Jennifer R
AU  - Ayers-Ringler JR
AD  - Neurobiology of Disease Program, Mayo Graduate School, Mayo Clinic, RochesterMN, 
      United States.
FAU - Biernacka, Joanna M
AU  - Biernacka JM
AD  - Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo 
      Clinic, RochesterMN, United States.
AD  - Division of Biomedical Statistics and Informatics, Mayo Clinic, RochesterMN, 
      United States.
FAU - Geske, Jennifer R
AU  - Geske JR
AD  - Division of Biomedical Statistics and Informatics, Mayo Clinic, RochesterMN, 
      United States.
FAU - Lindberg, Daniel R
AU  - Lindberg DR
AD  - Neurobiology of Disease Program, Mayo Graduate School, Mayo Clinic, RochesterMN, 
      United States.
FAU - McElroy, Susan L
AU  - McElroy SL
AD  - Lindner Center of HOPE, MasonOH, United States.
AD  - Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati 
      College of Medicine, CincinnatiOH, United States.
FAU - Frye, Mark A
AU  - Frye MA
AD  - Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo 
      Clinic, RochesterMN, United States.
FAU - Choi, Doo-Sup
AU  - Choi DS
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      RochesterMN, United States.
AD  - Neurobiology of Disease Program, Mayo Graduate School, Mayo Clinic, RochesterMN, 
      United States.
AD  - Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo 
      Clinic, RochesterMN, United States.
FAU - Veldic, Marin
AU  - Veldic M
AD  - Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo 
      Clinic, RochesterMN, United States.
LA  - eng
PT  - Journal Article
DEP - 20170721
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC5520464
OTO - NOTNLM
OT  - SLC1A2 (EAAT2)
OT  - addiction
OT  - biomarkers
OT  - bipolar disorder
OT  - glutamate
OT  - methylation
EDAT- 2017/08/09 06:00
MHDA- 2017/08/09 06:01
PMCR- 2017/01/01
CRDT- 2017/08/09 06:00
PHST- 2017/03/31 00:00 [received]
PHST- 2017/07/06 00:00 [accepted]
PHST- 2017/08/09 06:00 [entrez]
PHST- 2017/08/09 06:00 [pubmed]
PHST- 2017/08/09 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2017.00217 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2017 Jul 21;11:217. doi: 10.3389/fncel.2017.00217. 
      eCollection 2017.