Supportive evidence for reduced expression of GNB1L in schizophrenia

Hiroki Ishiguro, Minori Koga, Yasue Horiuchi, Emiko Noguchi, Miyuki Morikawa, Yoshimi Suzuki, Makoto Arai, Kazuhiro Niizato, Shyuji Iritani, Masanari Itokawa, Toshiya Inada, Nakao Iwata, Norio Ozaki, Hiroshi Ujike, Hiroshi Kunugi, Tsukasa Sasaki, Makoto Takahashi, Yuichiro Watanabe, Toshiyuki Someya, Akiyoshi KakitaHitoshi Takahashi, Hiroyuki Nawa, Tadao Arinami

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Abstract

Background: Chromosome 22q11 deletion syndrome (22q11DS) increases the risk of development of schizophrenia more than 10 times compared with that of the general population, indicating that haploinsufficiency of a subset of the more than 20 genes contained in the 22q11DS region could increase the risk of schizophrenia. In the present study, we screened for genes located in the 22q11DS region that are expressed at lower levels in postmortem prefrontal cortex of patients with schizophrenia than in those of controls. Methods: Gene expression was screened by Illumina Human-6 Expression BeadChip arrays and confirmed by real-time reverse transcription-polymerase chain reaction assays and Western blot analysis. Results: Expression of GNB1L was lower in patients with schizophrenia than in control subjects in both Australian (10 schizophrenia cases and 10 controls) and Japanese (43 schizophrenia cases and 11 controls) brain samples. TBX1 could not be evaluated due to its low expression levels. Expression levels of the other genes were not significantly lower in patients with schizophrenia than in control subjects. Association analysis of tag single-nucleotide polymorphisms in the GNB1L gene region did not confirm excess homozygosity in 1918 Japanese schizophrenia cases and 1909 Japanese controls. Haloperidol treatment for 50 weeks increased Gnb1l gene expression in prefrontal cortex of mice. Conclusions: Taken together with the impaired prepulse inhibition observed in heterozygous Gnb1l knockout mice reported by the previous study, the present findings support assertions that GNB1L is one of the genes in the 22q11DS region responsible for increasing the risk of schizophrenia.

Original languageEnglish
Pages (from-to)756-765
Number of pages10
JournalSchizophrenia Bulletin
Volume36
Issue number4
DOIs
Publication statusPublished - 01-07-2010

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All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health

Cite this

Ishiguro, H., Koga, M., Horiuchi, Y., Noguchi, E., Morikawa, M., Suzuki, Y., Arai, M., Niizato, K., Iritani, S., Itokawa, M., Inada, T., Iwata, N., Ozaki, N., Ujike, H., Kunugi, H., Sasaki, T., Takahashi, M., Watanabe, Y., Someya, T., ... Arinami, T. (2010). Supportive evidence for reduced expression of GNB1L in schizophrenia. Schizophrenia Bulletin, 36(4), 756-765. https://doi.org/10.1093/schbul/sbn160