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

被引：23

作者：

Anitha, Ayyappan ^{[1
]}

Nakamura, Kazuhiko ^{[1
]}

Yamada, Kazuo ^{[2
]}

Iwayama, Yoshimi ^{[2
]}

Toyota, Tomoko ^{[2
]}

Takei, Nori ^{[3
]}

Iwata, Yasuhide ^{[1
]}

Suzuki, Katsuaki ^{[3
]}

Sekine, Yoshimoto ^{[1
]}

Matsuzaki, Hideo ^{[4
]}

Kawai, Masayoshi ^{[1
]}

Thanseem, Ismail ^{[1
]}

Miyoshi, Ko ^{[5
]}

Katayama, Taiichi ^{[6
]}

Matsuzaki, Shinsuke ^{[4
,7
,8
]}

Baba, Kousuke ^{[9
]}

Honda, Akiko ^{[10
]}

Hattori, Tsuyoshi ^{[7
,8
]}

Shimizu, Shoko ^{[7
,8
]}

Kumamoto, Natsuko ^{[7
,8
]}

Kikuchi, Mitsuru ^{[11
]}

Tohyama, Masaya ^{[4
,7
,8
]}

Yoshikawa, Takeo ^{[2
]}

Mori, Norio ^{[1
,3
]}

机构：

[1] Hamamatsu Univ Sch Med, Dept Psychiat & Neurol, Hamamatsu, Shizuoka 4313192, Japan

[2] RIKEN Brain Sci Inst, Lab Mol Psychiat, Saitama, Japan

[3] Hamamatsu Univ Sch Med, Ctr Child Mental Dev, Hamamatsu, Shizuoka 4313192, Japan

[4] Osaka Univ, Grad Sch Med, Ctr Child Mental Dev, Osaka, Japan

[5] Okayama Univ, Dept Brain Sci, Grad Sch Med & Dent, Okayama, Japan

[6] Hamamatsu Univ Sch Med, Dept Anat & Neurosci, Hamamatsu, Shizuoka 4313192, Japan

[7] Osaka Univ, Grad Sch Med, Dept Anat & Neurosci, Osaka, Japan

[8] 21st Century COE Program, Osaka, Japan

[9] Kobe Univ, Sch Med, Dept Anat & Dev Neurobiol, Kobe, Hyogo 650, Japan

[10] Tanabe Seiyaku Co Ltd, Pharmacol Res Lab, Osaka, Japan

[11] Kanazawa Univ, Grad Sch Med Sci, Dept Psychiat & Neurobiol, Kanazawa, Ishikawa, Japan

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2009年 / 150B卷 / 07期

关键词：

DISC1; PCNT2; DBZ; schizophrenia; bipolar disorder; DISC1; GENE; DISRUPTED-IN-SCHIZOPHRENIA-1; POSITIVE ASSOCIATION; BRAIN MORPHOLOGY; RISK ALLELE; CENTROSOME; TRANSLOCATION; PHENOTYPES; BINDING; SUSCEPTIBILITY;

D O I：

10.1002/ajmg.b.30926

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：967 / 976

页数：10

共 58 条

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