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Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia

Molecular Psychiatry volume 10, pages 1045–1055 (2005)Cite this article

Abstract

We previously reported that expression level of LIM (ENH, PDLIM5) was significantly and commonly increased in the brains of patients with bipolar disorder, schizophrenia, and major depression. Expression of LIM was decreased in the lymphoblastoid cells derived from patients with bipolar disorders and schizophrenia. LIM protein reportedly plays an important role in linking protein kinase C with calcium channel. These findings suggested the role of LIM in the pathophysiology of bipolar disorder and schizophrenia. To further investigate the role of LIM in these mental disorders, we performed a replication study of gene expression analysis and performed genetic association studies. Upregulation of LIM was confirmed in the independent sample set obtained from Stanley Array Collection. No effect of sample pH or medication was observed. Genetic association study revealed the association of single nucleotide polymorphism (SNP)1 (rs10008257) with bipolar disorder. In an independent sample set, SNP2 (rs2433320) close to SNP1 was associated with bipolar disorder. In total samples, haplotype of these two SNPs was associated with bipolar disorder. No association was observed in case–control analysis and family-based association analysis in schizophrenia. These results suggest that SNPs in the upstream region of LIM may confer the genetic risk for bipolar disorder.

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Acknowledgements

Postmortem brain tissue was donated by the Stanley Medical Research Institute's brain collection courtesy of Drs Michael B Knable, E Fuller Torrey, Maree J Webster, Serge Weis, and Robert H Yolken. This study was supported by a grant from the Lab. for Molecular Dynamics of Mental Disorders (T Kato). We thank all the volunteers who participated in this study. We also appreciate the continuous support by the Research Resource Center, RIKEN Brain Science Institute. We are grateful for the valuable discussion to Dr Tadao Arinami (University of Tsukuba).

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Authors and Affiliations

  1. Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Wako-shi, Saitama, Japan

    T Kato, C Kakiuchi & K Iwamoto

  2. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako-shi, Saitama, Japan

    Y Iwayama, K Yamada & T Yoshikawa

  3. Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Y Minabe, K Nakamura & N Mori

  4. Biwako Hospital, Otsu, Japan

    K Fujii

  5. Department of Psychiatry and Genome Research Center, Teikyo University School of Medicine, Tokyo, Japan

    S Nanko

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  1. T Kato
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  2. Y Iwayama
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Correspondence to T Kato.

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Kato, T., Iwayama, Y., Kakiuchi, C. et al. Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia. Mol Psychiatry 10, 1045–1055 (2005). https://doi.org/10.1038/sj.mp.4001719

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  • DOI: https://doi.org/10.1038/sj.mp.4001719

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