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.
