Gene and Expression Analyses Reveal Enhanced Expression of Pericentrin 2 (PCNT2) in Bipolar Disorder

Anitha, Ayyappan; Nakamura, Kazuhiko; Yamada, Kazuo; Iwayama, Yoshimi; Toyota, Tomoko; Takei, Nori; Iwata, Yasuhide; Suzuki, Katsuaki; Sekine, Yoshimoto; Matsuzaki, Hideo; Kawai, Masayoshi; Miyoshi, Ko; Katayama, Taiichi; Matsuzaki, Shinsuke; Baba, Kousuke; Honda, Akiko; Hattori, Tsuyoshi; Shimizu, Shoko; Kumamoto, Natsuko; Tohyama, Masaya; Yoshikawa, Takeo; Mori, Norio

doi:10.1016/j.biopsych.2007.07.010

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Volume 63, Issue 7 , Pages 678-685, 1 April 2008

Gene and Expression Analyses Reveal Enhanced Expression of Pericentrin 2 (PCNT2) in Bipolar Disorder

Ayyappan Anitha
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Kazuhiko Nakamura
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan
- Address reprint requests to Kazuhiko Nakamura, M.D., Ph.D., Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan
Kazuo Yamada
- Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan
Yoshimi Iwayama
- Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan
Tomoko Toyota
- Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan
Nori Takei
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Yasuhide Iwata
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Katsuaki Suzuki
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Yoshimoto Sekine
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Hideo Matsuzaki
- The Osaka-Hamamatsu Joint Research, Center for Child Mental Development, Graduate School of Medicine, Osaka University, Japan
Masayoshi Kawai
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Ko Miyoshi
- Department of Brain Science, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan
Taiichi Katayama
- Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine, Hamamatsu, Japan
Shinsuke Matsuzaki
- The Osaka-Hamamatsu Joint Research, Center for Child Mental Development, Graduate School of Medicine, Osaka University, Japan
- Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Japan
- The 21st Century COE program, Japan
Kousuke Baba
- Department of Anatomy and Development Neurobiology, School of Medicine, Kobe University, Kobe, Japan.
Akiko Honda
- Pharmacology Research Laboratory, Tanabe Seiyaku, Osaka, Japan
Tsuyoshi Hattori
- Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Japan
- The 21st Century COE program, Japan
Shoko Shimizu
- Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Japan
- The 21st Century COE program, Japan
Natsuko Kumamoto
- Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Japan
- The 21st Century COE program, Japan
Masaya Tohyama
- The Osaka-Hamamatsu Joint Research, Center for Child Mental Development, Graduate School of Medicine, Osaka University, Japan
- Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Japan
- The 21st Century COE program, Japan
Takeo Yoshikawa
- Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan
Norio Mori
- Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Received 17 April 2007; received in revised form 13 July 2007; accepted 13 July 2007. published online 21 September 2007.

Background

DISC1 has been suggested as a causative gene for psychoses in a large Scottish kindred. PCNT2 has recently been identified as an interacting partner of DISC1. In this study, we investigated the role of PCNT2 in bipolar disorder, by gene expression analysis and genetic association study.

Methods

By TaqMan real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), we examined the messenger RNA (mRNA) levels of PCNT2 in the postmortem prefrontal cortex of bipolar disorder (n = 34), schizophrenia (n = 31), and control subjects (n = 32), obtained from Stanley Array Collection. We also compared the mRNA levels of PCNT2 in the peripheral blood lymphocytes of bipolar disorder (n = 21), schizophrenia (n = 21), depression (n = 33), and control subjects (n = 57). For the association study, 23 single nucleotide polymorphisms (SNPs) were analyzed in 285 bipolar disorder patients and 287 age-and gender-matched control subjects, all of Japanese origin. The genotypes were determined by TaqMan assay.

Results

Significantly higher expression of PCNT2 was observed in the brain samples of bipolar group, compared with the control (p = .001) and schizophrenia (p = .018) groups. In the peripheral blood lymphocytes also, a significantly higher expression of PCNT2 was observed in the bipolar group, compared with the control subjects (p = .043). However, none of the SNPs analyzed in our study showed a significant association with bipolar disorder; a weak tendency toward association was observed for two intronic SNPs.