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.
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.
Anitha
Ayyappan
A
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Nakamura
Kazuhiko
K
Yamada
Kazuo
K
Iwayama
Yoshimi
Y
Toyota
Tomoko
T
Takei
Nori
N
Iwata
Yasuhide
Y
Suzuki
Katsuaki
K
Sekine
Yoshimoto
Y
Matsuzaki
Hideo
H
Kawai
Masayoshi
M
Thanseem
Ismail
I
Miyoshi
Ko
K
Katayama
Taiichi
T
Matsuzaki
Shinsuke
S
Baba
Kousuke
K
Honda
Akiko
A
Hattori
Tsuyoshi
T
Shimizu
Shoko
S
Kumamoto
Natsuko
N
Kikuchi
Mitsuru
M
Tohyama
Masaya
M
Yoshikawa
Takeo
T
Mori
Norio
N
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*
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