Positive association of Phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia

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

研究成果: Contribution to journalArticle査読

14 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)850-858
ページ数9
ジャーナルAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
156
7
DOI
出版ステータス出版済み - 12 2011

All Science Journal Classification (ASJC) codes

  • 遺伝学(臨床)
  • 精神医学および精神衛生
  • 細胞および分子神経科学

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