title: 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.
abstract: 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.
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Nori
authors.initials: N
authors.lastname: Takei
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kawai
authors.forename: Ismail
authors.initials: I
authors.lastname: Thanseem
authors.forename: Ko
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Matsuzaki
authors.forename: Kousuke
authors.initials: K
authors.lastname: Baba
authors.forename: Akiko
authors.initials: A
authors.lastname: Honda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hattori
authors.forename: Shoko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kumamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
mesh_terms: D000328:Adult; D000483:Alleles; D000941:Antigens / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011485:Protein Binding; D012559:Schizophrenia / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000941:Antigens; D002352:Carrier Proteins; C412476:DISC1 protein, human; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C475725:ZNF365 protein, human; C086178:pericentrin