Document Detail

Positive association of Phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia.
MedLine Citation:
PMID:  21898905     Owner:  NLM     Status:  In-Data-Review    
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. © 2011 Wiley-Liss, Inc.
Xiangdong Deng; Hiromi Takaki; Lixiang Wang; Tosihide Kuroki; Tatsuo Nakahara; Kijiro Hashimoto; Hideaki Ninomiya; Tadao Arinami; Toshiya Inada; Hiroshi Ujike; Masanari Itokawa; Mamoru Tochigi; Yuichiro Watanabe; Toshiyuki Someya; Hiroshi Kunugi; Nakao Iwata; Norio Ozaki; Hiroki Shibata; Yasuyuki Fukumaki
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Publication Detail:
Type:  Journal Article     Date:  2011-08-23
Journal Detail:
Title:  American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics     Volume:  156     ISSN:  1552-485X     ISO Abbreviation:  Am. J. Med. Genet. B Neuropsychiatr. Genet.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-09-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101235742     Medline TA:  Am J Med Genet B Neuropsychiatr Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  850-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
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