Association Studies and Gene Expression Analyses of the DISC1-Interacting Molecules, Pericentrin 2 (PCNT2) and DISC1-Binding Zinc Finger Protein (DBZ), With Schizophrenia and With Bipolar Disorder
Association Studies and Gene Expression Analyses of the DISC1-Interacting Molecules, Pericentrin 2 (PCNT2) and DISC1-Binding Zinc Finger Protein (DBZ), With Schizophrenia and With Bipolar Disorder
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DOI：
10.1002/ajmg.b.30926
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发表时间：
2009-10-05
影响因子：
2.8
通讯作者：
Mori, Norio
中科院分区：
文献类型：
--
作者：
Anitha, Ayyappan;Nakamura, Kazuhiko;Mori, Norio
精神分裂症1（DISC 1）及其分子级联反应与重性精神病的病理生理学有关。以前，我们确定了围中心蛋白2（PCNT 2）和DISC 1结合锌指蛋白（DBZ）作为DISC 1的结合伴侣;此外，我们观察到PCNT 2在死后大脑和双相情感障碍患者的淋巴细胞中的表达升高，与对照组相比。在这里，我们研究了PCNT 2与精神分裂症在日本队列的病例对照研究。我们还研究了DBZ与精神分裂症和双相情感障碍的关系，并比较了DBZ在精神分裂症，双相情感障碍和对照样本的死后大脑中的mRNA水平。应用180例精神分裂症患者和201例正常对照的DNA，对PCNT 2和DBZ基因与精神分裂症的关联性进行了研究。研究人员从238名双相情感障碍患者和240名年龄和性别相匹配的对照者的DNA中检测了DBZ与双相情感障碍的关系。我们观察到PCNT 2 SNP rs 2249057、rs 2268524和rs 2073380（Ser/Arg）与精神分裂症的显著等位基因和基因型关联; rs 2249057（P=0.002）的关联经得起多重检验校正。几个两个SNP-和三个SNP-单倍型显示出显着的关联;涉及rs 2249057的单倍型的关联经得起多次检验校正。DBZ与精神分裂症或双相情感障碍没有观察到任何关联;此外，对照组、精神分裂症和双相死后大脑的DBZ mRNA水平之间没有显著差异。我们建议PCNT 2在精神分裂症的发病机制中可能发挥作用。PCNT 2是微管组织所必需的中心体蛋白，其缺失可能导致神经发育异常。(C)2009 Wiley-Liss，Inc.
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. (C) 2009 Wiley-Liss, Inc.