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The Gem interacting protein (GMIP) gene is associated with major depressive disorder

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Abstract

Major depressive disorder (MDD) is a mood disorder with a significant heritable component. Structural neuronal impairment has been considered to be implicated in MDD, as it leads to brain morphological alterations such as hippocampal atrophy. The Gem interacting protein, GMIP, is a novel Rho GTPase-activating protein known to play important roles in neurite growth and axonal guidance. We examined the GMIP gene for possible association in a Japanese sample of 164 patients with MDD and 164 controls matched for sex. We found a significant association with MDD for one single nucleotide polymorphism (SNP) (−525G/A) located on the 5′-upstream region of the GMIP gene (p=0.039, odds ratio 1.66, 95% CI 1.05–2.69) and stronger evidence for association in a multimarker haplotype analysis (p=0.004). We then performed a promoter-luciferase reporter assay; the promoter activity for −525A allele, which was in excess in the MDD patients, was significantly decreased compared with the −525G allele in transient transfection experiments using three types of cell lines. Our results suggest that genetic variations in the GMIP gene can confer susceptibility to MDD, and the associated promoter SNP might play a role in the transcriptional regulation of the GMIP gene. Further study needs to be undertaken to validate the association between the GMIP gene and MDD.

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Acknowledgements

The authors thank Tomoko Shizuno and Reiko Fujita for technical assistance. This work was supported by grants-in-aid from the Japanese Ministry of Health, Labor and Welfare, the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Uehara Memorial Foundation, Takeda Science Foundation, and Japan Foundation for Neuroscience and Mental Health. Experiments comply with the current laws in Japan.

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Authors and Affiliations

  1. Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Japan, 4-1-1, Ogawahigashicho, Kodaira, Tokyo, 187-8502, Japan

    Kazuyuki Tadokoro, Ryota Hashimoto & Hiroshi Kunugi

  2. Yokohama Shinryo Clinic, Yokohama, Kanagawa, 221-0385, Japan

    Masahiko Tatsumi

  3. Department of Psychiatry, Showa University School of Medicine, Tokyo, 142-8666, Japan

    Masahiko Tatsumi & Kunitoshi Kamijima

  4. Showa University Karasuyama Hospital, Tokyo, 157-8577, Japan

    Asako Kosuga

Authors
  1. Kazuyuki Tadokoro
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  2. Ryota Hashimoto
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  3. Masahiko Tatsumi
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  4. Asako Kosuga
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  5. Kunitoshi Kamijima
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  6. Hiroshi Kunugi
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Correspondence to Ryota Hashimoto.

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Tadokoro, K., Hashimoto, R., Tatsumi, M. et al. The Gem interacting protein (GMIP) gene is associated with major depressive disorder. Neurogenetics 6, 127–133 (2005). https://doi.org/10.1007/s10048-005-0003-3

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  • DOI: https://doi.org/10.1007/s10048-005-0003-3

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