Epigenetic regulation on GABRB2 isoforms expression: developmental variations and disruptions in psychotic disorders
Language: 
English
Short Title: 
Epigenetic regulation on GABRB2 isoforms expression
Abstract: 

INTRODUCTION: To improve the understanding of psychotic abnormalities and their non-Mendelian inheritance patterns, the epigenetic regulation of the psychotic disorder-associated GABRB2, gene for the type A ?-aminobutyric acid receptor ?(2)-subunit, was investigated. METHODS: Expression of GABRB2, and the epigenetic regulatory enzymes histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) in mouse and postmortem human brains was analyzed using real-time PCR. RESULTS: Results showed that expression of GABRB2 isoforms significantly increased over time in both mouse and human, especially for the long splicing isoform. In the brains of non-psychiatric controls (CON), a significant positive correlation of GABRB2 expression with age was observed in individuals with MM genotypes of the single nucleotide polymorphisms (SNPs) rs187269 and rs1816072. This was reversed to a significant negative correlation in schizophrenics (SCZ). A similar reversal was also displayed by bipolar disorder (BPD) patients. In parallel, a significant co-variation of HDAC1 with GABRB2 expression observed in CON remained significant in BPD but not in SCZ; comparably, a significant co-variation of HDAC2 with GABRB2 expression observed in CON became non-significant in both SCZ and BPD. Moreover, co-variations of DNMT1 and DNMT3B with GABRB2, not observable in CON, became significant in BPD. CONCLUSION: These findings demonstrated that GABRB2 expression was under epigenetic regulation that varied with development, genotype and disease status, and these regulatory mechanisms were observably disrupted in SCZ and BPD. This study provided insight into the complex inheritance patterns of psychiatric disorders, and pointed to the involvement of epigenetic dysregulation in the disease process of major psychotic disorders.

Author(s): 
Zhao, Cunyou
Wang, Feng
Pun, Frank W.
Mei, Lingling
Ren, Lihuan
Yu, Zhiliang
Ng, Siu-Kin
Chen, Jianhuan
Tsang, Shui-Ying
Xue, Hong
Item Type: 
Journal Article
Publication Title: 
Schizophrenia Research
Journal Abbreviation: 
Schizophr. Res.
Publication Date: 
2012-02
Publication Year: 
2012
Pages: 
260-266
Volume: 
134
Issue: 
3-Feb
ISSN: 
1573-2509
DOI: 
10.1016/j.schres.2011.11.029
Library Catalog: 
PubMed
Extra: 
PMID: 22206711

Turabian/Chicago Citation

Cunyou Zhao, Feng Wang, Frank W. Pun, Lingling Mei, Lihuan Ren, Zhiliang Yu, Siu-Kin Ng, Jianhuan Chen, Shui-Ying Tsang and Hong Xue. 2012-02. "Epigenetic regulation on GABRB2 isoforms expression: developmental variations and disruptions in psychotic disorders." Schizophrenia Research 134: 3-Feb: 260-266. 10.1016/j.schres.2011.11.029.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.schres.2011.11.029 | issn = 1573-2509 | volume = 134 | pages = 260-266 | last = Zhao | first = Cunyou | coauthors = Wang, Feng, Pun, Frank W., Mei, Lingling, Ren, Lihuan, Yu, Zhiliang, Ng, Siu-Kin, Chen, Jianhuan, Tsang, Shui-Ying, Xue, Hong | title = Epigenetic regulation on GABRB2 isoforms expression: developmental variations and disruptions in psychotic disorders | journal = Schizophrenia Research | date = 2012-02 | pmid = | pmc = }} </ref>