title: Positive association of phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia.
abstract: 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 4 hr 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.
authors: Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors: Xiangdong
authors: X
authors: Deng
authors: Hiromi
authors: H
authors: Takaki
authors: Lixiang
authors: L
authors: Wang
authors: Tosihide
authors: T
authors: Kuroki
authors: Tatsuo
authors: T
authors: Nakahara
authors: Kijiro
authors: K
authors: Hashimoto
authors: Hideaki
authors: H
authors: Ninomiya
authors: Tadao
authors: T
authors: Arinami
authors: Toshiya
authors: T
authors: Inada
authors: Hiroshi
authors: H
authors: Ujike
authors: Masanari
authors: M
authors: Itokawa
authors: Mamoru
authors: M
authors: Tochigi
authors: Yuichiro
authors: Y
authors: Watanabe
authors: Toshiyuki
authors: T
authors: Someya
authors: Hiroshi
authors: H
authors: Kunugi
authors: Nakao
authors: N
authors: Iwata
authors: Norio
authors: N
authors: Ozaki
authors: Hiroki
authors: H
authors: Shibata
authors: Yasuyuki
authors: Y
authors: Fukumaki
mesh_terms: D000328:Adult; D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010622:Phencyclidine / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*; D010959:Tissue Plasminogen Activator / Q000235:genetics*
chemical_list: D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D010959:Tissue Plasminogen Activator; D010622:Phencyclidine