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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
Author(s) -
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
Publication year - 2009
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30926
Subject(s) - disc1 , zinc finger , gene , biology , schizophrenia (object oriented programming) , genetics , psychology , transcription factor , psychiatry
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. © 2009 Wiley‐Liss, Inc.