Anitha Ayyappan, Nakamura Kazuhiko, Yamada Kazuo, Iwayama Yoshimi, Toyota Tomoko, Takei Nori, Iwata Yasuhide, Suzuki Katsuaki, Sekine Yoshimoto, Matsuzaki Hideo, Kawai Masayoshi, Thanseem Ismail, Miyoshi Ko, Katayama Taiichi, Matsuzaki Shinsuke, Baba Kousuke, Honda Akiko, Hattori Tsuyoshi, Shimizu Shoko, Kumamoto Natsuko, Kikuchi Mitsuru, Tohyama Masaya, Yoshikawa Takeo, Mori Norio
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Am J Med Genet B Neuropsychiatr Genet. 2009 Oct 5;150B(7):967-76. doi: 10.1002/ajmg.b.30926.
Disrupted-in-Schizophrenia 1 (DISC1) and its molecular cascade have been implicated in the pathophysiology of major psychoses. Previously, we identified pericentrin 2 (PCNT2) and DISC1-binding zinc finger protein (DBZ) as binding partners of DISC1; further, we observed elevated expression of PCNT2 in the postmortem brains and in the lymphocytes of bipolar disorder patients, compared to controls. Here, we examined the association of PCNT2 with schizophrenia in a case-control study of Japanese cohorts. We also examined the association of DBZ with schizophrenia and with bipolar disorder, and compared the mRNA levels of DBZ in the postmortem brains of schizophrenia, bipolar and control samples. DNA from 180 schizophrenia patients 201 controls were used for the association study of PCNT2 and DBZ with schizophrenia. Association of DBZ with bipolar disorder was examined in DNA from 238 bipolar patients and 240 age- and gender-matched controls. We observed significant allelic and genotypic associations of the PCNT2 SNPs, rs2249057, rs2268524, and rs2073380 (Ser/Arg) with schizophrenia; the association of rs2249057 (P = 0.002) withstand multiple testing correction. Several two SNP- and three SNP-haplotypes showed significant associations; the associations of haplotypes involving rs2249057 withstand multiple testing correction. No associations were observed for DBZ with schizophrenia or with bipolar disorder; further, there was no significant difference between the DBZ mRNA levels of control, schizophrenia and bipolar postmortem brains. We suggest a possible role of PCNT2 in the pathogenesis of schizophrenia. Abnormalities of PCNT2, the centrosomal protein essential for microtubule organization, may be suggested to lead to neurodevelopmental abnormalities.
精神分裂症断裂基因1（DISC1）及其分子级联反应与主要精神疾病的病理生理学有关。此前，我们鉴定了中心粒外周蛋白2（PCNT2）和DISC1结合锌指蛋白（DBZ）为DISC1的结合伴侣；此外，我们观察到与对照组相比，双相情感障碍患者的死后大脑和淋巴细胞中PCNT2的表达升高。在此，我们在一项日本队列的病例对照研究中检验了PCNT2与精神分裂症的关联。我们还检验了DBZ与精神分裂症和双相情感障碍的关联，并比较了精神分裂症、双相情感障碍和对照样本的死后大脑中DBZ的mRNA水平。来自180名精神分裂症患者和201名对照的DNA用于PCNT2和DBZ与精神分裂症的关联研究。在来自238名双相情感障碍患者和240名年龄及性别匹配对照的DNA中检验DBZ与双相情感障碍的关联。我们观察到PCNT2单核苷酸多态性（SNP）rs2249057、rs2268524和rs2073380（丝氨酸/精氨酸）与精神分裂症存在显著的等位基因和基因型关联；rs2249057的关联（P = 0.002）经多重检验校正后仍然显著。几个双SNP和三SNP单倍型显示出显著关联；涉及rs2249057的单倍型关联经多重检验校正后仍然显著。未观察到DBZ与精神分裂症或双相情感障碍存在关联；此外，对照、精神分裂症和双相情感障碍死后大脑的DBZ mRNA水平之间无显著差异。我们认为PCNT2在精神分裂症发病机制中可能发挥作用。PCNT2是微管组织所必需的中心体蛋白，其异常可能导致神经发育异常。
