Gene expression and association analyses of the phosphodiesterase 4B (PDE4B) gene in major depressive disorder in the Japanese population

Authors

  • Shusuke Numata,

    Corresponding author
    1. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
    • Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
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  • Jun-ichi Iga,

    1. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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  • Masahito Nakataki,

    1. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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  • Shin'Ya Tayoshi,

    1. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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  • Kyoko Taniguchi,

    1. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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  • Satsuki Sumitani,

    1. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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  • Masahito Tomotake,

    1. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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  • Toshihito Tanahashi,

    1. Division of Genetic Information, Institute for Genome Research, The University of Tokushima Graduate School, Tokushima, Japan
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  • Mitsuo Itakura,

    1. Division of Genetic Information, Institute for Genome Research, The University of Tokushima Graduate School, Tokushima, Japan
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  • Yoko Kamegaya,

    1. Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Masahiko Tatsumi,

    1. Yokohama Shinryo Clinic, Kanagawa, Japan
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  • Akira Sano,

    1. Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan
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  • Takashi Asada,

    1. Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
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  • Hiroshi Kunugi,

    1. Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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  • Shu-ichi Ueno,

    1. Department of Community and Psychiatric Nursing, School of Health Sciences, The University of Tokushima Graduate School, Tokushima, Japan
    2. Department of Neuropsychiatry, Neuroscience, Ehime University Graduate School of Medicine, Ehime, Japan
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  • Tetsuro Ohmori

    1. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
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  • Please cite this article as follows: Numata S, Iga J-i, Nakataki M, Tayoshi S, Taniguchi K, Sumitani S, Tomotake M, Tanahashi T, Itakura M, Kamegaya Y, Tatsumi M, Sano A, Asada T, Kunugi H, Ueno S-i, Ohmori T. 2008. Gene Expression and Association Analyses of the Phosphodiesterase 4B (PDE4B) Gene in Major Depressive Disorder in the Japanese Population. Am J Med Genet Part B 150B:527–534.

Abstract

The phosphodiesterase 4B (PDE4B) interacts with disrupted-in-schizophrenia 1 (DISC1), which is a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). PDE4B is also important in the regulation of cAMP signaling, a second messenger implicated in learning, memory, and mood. In this study, we determined mRNA expression levels of the PDE4B gene in the peripheral blood leukocytes of patients with MDD and control subjects (n = 33, each). Next we performed two-stage case-controlled association analyses (first set; case = 174, controls = 348; second set; case = 481, controls = 812) in the Japanese population to determine if the PDE4B gene is implicated in MDD. In the leukocytes, a significantly higher expression of the PDE4B mRNA was observed in the drug-naïve MDD patients compared with control subjects (P < 0.0001) and the expression of the MDD patients significantly decreased after antidepressant treatment (P = 0.030). In the association analysis, we observed significant allelic associations of four SNPs (the most significant, rs472952; P = 0.002) and a significant haplotypic association (permutation P = 0.019) between the PDE4B gene and MDD in the first-set samples. However, we could not confirm these significant associations in the following independent second-set of samples. Our results suggest that the PDE4B gene itself does not link to MDD but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD. © 2008 Wiley-Liss, Inc.

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