Cited by 112Schizophrenia research and treatmentChromatin Remodeling and CancerGenetics and Neurodevelopmental Disorders

Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia

Koga, Minori, Ishiguro, Hiroki, Yazaki, Saori, Horiuchi, Yasue, Arai, Makoto, Niizato, Kazuhiro, Iritani, Shuji, Itokawa, Masanari +15 more·2009·Human Molecular Genetics

Abstract

Chromatin remodeling may play a role in the neurobiology of schizophrenia and the process, therefore, may be considered as a therapeutic target. The SMARCA2 gene encodes BRM in the SWI/SNF chromatin-remodeling complex, and associations of single nucleotide polymorphisms (SNPs) to schizophrenia were found in two linkage disequilibrium blocks in the SMARCA2 gene after screening of 11 883 SNPs (rs2296212; overall allelic P = 5.8 x 10(-5)) and subsequent screening of 22 genes involved in chromatin remodeling (rs3793490; overall allelic P = 2.0 x 10(-6)) in a Japanese population. A risk allele of a missense polymorphism (rs2296212) induced a lower nuclear localization efficiency of BRM, and risk alleles of intronic polymorphisms (rs3763627 and rs3793490) were associated with low SMARCA2 expression levels in the postmortem prefrontal cortex. A significant correlation in the fold changes of gene expression from schizophrenic prefrontal cortex (from the Stanley Medical Research Institute online genomics database) was seen with suppression of SMARCA2 in transfected human cells by specific siRNA, and of orthologous genes in the prefrontal cortex of Smarca2 knockout mice. Smarca2 knockout mice showed impaired social interaction and prepulse inhibition. Psychotogenic drugs lowered Smarca2 expression while antipsychotic drugs increased it in the mouse brain. These findings support the existence of a role for BRM in the pathophysiology of schizophrenia.

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Crossref · 10.1093/hmg/ddp166

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Authors
Koga, M., Ishiguro, H., Yazaki, S., Horiuchi, 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., Kakita, A., Takahashi, H., Nawa, H., Muchardt, C., Yaniv, M., & Arinami, T.
Affiliations
  • University of Tsukuba (JP)
  • Tokyo Institute of Psychiatry (JP)
  • Tokyo Metropolitan Matsuzawa Hospital (JP)
  • Japan Science and Technology Agency (JP)
  • Seiwa Hospital (JP)
  • Fujita Health University (JP)
  • Nagoya University (JP)
  • Okayama University (JP)
  • National Center of Neurology and Psychiatry (JP)
  • The University of Tokyo (JP)
  • Niigata University (JP)
  • Brain Research Institute, Niigata University (JP)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Arinami, Tadao
Venue
Human Molecular Genetics
Published
2009-04-10
Volume
18
Issue
13
Pages
2483-2494
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W2170353505
Cited by
112
References
56
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 10 · 2019: 12 · 2018: 7 · 2017: 7 · 2016: 1 · 2015: 7 · 2014: 8 · 2013: 10 · 2012: 10
FWCI
5.57
Type
journal article
Language
en
Open access
closed
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • National Institute on Alcohol Abuse and Alcoholism
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
SMARCA2, BRM, SWI/SNF complex, schizophrenia, single nucleotide polymorphisms, genetic association, prefrontal cortex gene expression, nuclear localization, prepulse inhibition, social interaction, antipsychotic drugs, risk alleles
MeSH terms
Adult, Aged, Amino Acid Sequence, Animals, Cell Line, Cell Nucleus, DNA-Binding Proteins, Female, Humans, Interpersonal Relations, Male, Mice, Inbred C57BL, Middle Aged, Molecular Sequence Data, Psychotropic Drugs, Schizophrenia, Transcription Factors, Cohort Studies, Gene Expression, Case-Control Studies, Sequence Alignment, Prefrontal Cortex, Mice, Knockout, Polymorphism, Single Nucleotide, Protein Transport, Chromatin Assembly and Disassembly, Asian People, Mice

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