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
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Biol Psychiatry. 2008 Apr 1;63(7):678-85. doi: 10.1016/j.biopsych.2007.07.010. Epub 2007 Sep 20.
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.
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.
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.
Our findings suggest that elevated levels of PCNT2 might be implicated in the pathophysiology of bipolar disorder.
在一个大型苏格兰家族中,DISC1被认为是精神病的致病基因。PCNT2最近被确定为DISC1的相互作用伴侣。在本研究中,我们通过基因表达分析和遗传关联研究,探讨了PCNT2在双相情感障碍中的作用。
通过TaqMan实时定量逆转录聚合酶链反应(qRT-PCR),我们检测了从斯坦利阵列库获得的双相情感障碍患者(n = 34)、精神分裂症患者(n = 31)和对照受试者(n = 32)的死后前额叶皮质中PCNT2的信使核糖核酸(mRNA)水平。我们还比较了双相情感障碍患者(n = 21)、精神分裂症患者(n = 21)、抑郁症患者(n = 33)和对照受试者(n = 57)外周血淋巴细胞中PCNT2的mRNA水平。对于关联研究,我们在285名双相情感障碍患者和287名年龄和性别匹配的对照受试者中分析了23个单核苷酸多态性(SNP),所有受试者均为日本血统。通过TaqMan分析确定基因型。
与对照组(p = .001)和精神分裂症组(p = .018)相比,双相情感障碍组脑样本中PCNT2的表达显著更高。在外周血淋巴细胞中,与对照受试者相比,双相情感障碍组中PCNT2的表达也显著更高(p = .043)。然而,我们研究中分析的SNP均未显示与双相情感障碍有显著关联;两个内含子SNP观察到有较弱的关联趋势。
我们的研究结果表明,PCNT2水平升高可能与双相情感障碍的病理生理学有关。