TY - JOUR
T1 - Positive association of Phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia
AU - Deng, Xiangdong
AU - Takaki, Hiromi
AU - Wang, Lixiang
AU - Kuroki, Tosihide
AU - Nakahara, Tatsuo
AU - Hashimoto, Kijiro
AU - Ninomiya, Hideaki
AU - Arinami, Tadao
AU - Inada, Toshiya
AU - Ujike, Hiroshi
AU - Itokawa, Masanari
AU - Tochigi, Mamoru
AU - Watanabe, Yuichiro
AU - Someya, Toshiyuki
AU - Kunugi, Hiroshi
AU - Iwata, Nakao
AU - Ozaki, Norio
AU - Shibata, Hiroki
AU - Fukumaki, Yasuyuki
PY - 2011/12
Y1 - 2011/12
N2 - As schizophrenia-like symptoms are produced by administration of phencyclidine (PCP), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, PCP-responsive genes could be involved in the pathophysiology of schizophrenia. We injected PCP to Wistar rats and isolated five different parts of the brain in 1 and 4hr after the injection. We analyzed the gene expression induced by the PCP treatment of these tissues using the AGILENT rat cDNA microarray system. We observed changes in expression level in 90 genes and 21 ESTs after the treatment. Out of the 10 genes showing >2-fold expressional change evaluated by qRT-PCR, we selected 7 genes as subjects for the locus-wide association study to identify susceptibility genes for schizophrenia in the Japanese population. In haplotype analysis, significant associations were detected in combinations of two SNPs of BTG2 (P=1.4×10-6), PDE4A (P=1.4×10-6), and PLAT (P=1×10-3), after false discovery rate (FDR) correction. Additionally, we not only successfully replicated the haplotype associations in PDE4A (P=6.8×10-12) and PLAT (P=0.015), but also detected single-point associations of one SNP in PDE4A (P=0.0068) and two SNPs in PLAT (P=0.0260 and 0.0104) in another larger sample set consisting of 2,224 cases and 2,250 controls. These results indicate that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese population.
AB - As schizophrenia-like symptoms are produced by administration of phencyclidine (PCP), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, PCP-responsive genes could be involved in the pathophysiology of schizophrenia. We injected PCP to Wistar rats and isolated five different parts of the brain in 1 and 4hr after the injection. We analyzed the gene expression induced by the PCP treatment of these tissues using the AGILENT rat cDNA microarray system. We observed changes in expression level in 90 genes and 21 ESTs after the treatment. Out of the 10 genes showing >2-fold expressional change evaluated by qRT-PCR, we selected 7 genes as subjects for the locus-wide association study to identify susceptibility genes for schizophrenia in the Japanese population. In haplotype analysis, significant associations were detected in combinations of two SNPs of BTG2 (P=1.4×10-6), PDE4A (P=1.4×10-6), and PLAT (P=1×10-3), after false discovery rate (FDR) correction. Additionally, we not only successfully replicated the haplotype associations in PDE4A (P=6.8×10-12) and PLAT (P=0.015), but also detected single-point associations of one SNP in PDE4A (P=0.0068) and two SNPs in PLAT (P=0.0260 and 0.0104) in another larger sample set consisting of 2,224 cases and 2,250 controls. These results indicate that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese population.
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U2 - 10.1002/ajmg.b.31233
DO - 10.1002/ajmg.b.31233
M3 - Article
C2 - 21898905
AN - SCOPUS:80052491357
SN - 1552-4841
VL - 156
SP - 850
EP - 858
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 7
ER -
