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Support for association of the PPP3CC gene with schizophrenia

Molecular Psychiatry volume 12, pages 891–893 (2007)Cite this article

Calcineurin is a calcium-dependent protein phosphatase that plays an important role in cellular responses and calcium signal transduction.1 Several studies have suggested that calcineurin is one of the key molecules in signal transduction in the brain and that dysfunction of calcineurin signaling could be linked to schizophrenia.2, 3 Calcineurin is a heteromeric protein complex consisting of a catalytic subunit (calcineurin A) and a regulatory subunit (calcineurin B).1, 4 PPP3CC encodes the calcineurin γ-catalytic subunit and is located on chromosome 8p21.3 within a few cM of markers reported to be linked to schizophrenia.5, 6, 7,10 Gerber et al.8 reported genetic associations of the PPP3CC gene with schizophrenia in populations from the United States and South Africa. However, only one replication study has been published, and these associations were not confirmed in 457 Japanese schizophrenic patients and 429 control subjects.9 HapMap data indicated that a haplotype block spans almost the entire PPP3CC region in Japanese and European populations. The single nucleotide polymorphism (SNP) haplotype reported to be associated with schizophrenia by Gerber et al.8 is located in the haplotype block. Therefore, we examined the associations in a large case–control study of 1645 schizophrenic patients and 1673 control subjects. This sample size has a power >0.98 to replicate the haplotypic association with the same magnitude as that reported by Gerber et al.,8 assuming an α value=0.05, two-tailed, a haplotype relative risk of 1.23, and haplotype frequency of 0.26 or effect size of 0.1. The haplotype frequency in the Japanese population was reported by Kinoshita et al.9

All subjects were of Japanese descent and were recruited from the main island of Japan. The study included 1645 unrelated patients with schizophrenia (mean age±s.d., 48.2±14.5 years; 899 men and 745 women) diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Control subjects were 1673 mentally healthy unrelated subjects (age, 47.9±14.3, 886 men and 787 women) without self-reported family histories of mental illness within second-degree relatives. The subjects studied by Kinoshita et al.9 were not included in the present study. The present study was approved by the Ethics Committees of the University of Tsukuba, Niigata University, Fujita Health University, Nagoya University, Okayama University and Teikyo University and all participants provided written informed consent. To rule out population stratification between patients and controls in the present study, 35 SNPs that are not in linkage disequilibrium (LD) with each other were genotyped in all samples and analyzed with the STRUCTURE program 2.0.5 No stratification was observed.

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Authors and Affiliations

  1. Department of Medical Genetics, Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Y Horiuchi, H Ishiguro, M Koga & T Arinami

  2. CREST, Japan Science and Technology Agency, Kawaguchi-shi, Saitama, Japan

    Y Horiuchi, H Ishiguro, M Koga & T Arinami

  3. Department of Psychiatry, Teikyo University School of Medicine, Chiba Medical Center, Anesaki, Ichihara-shi, Chiba, Japan

    T Inada

  4. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    N Iwata

  5. Department of Psychiatry, School of Medicine, Nagoya University, Nagoya, Aichi, Japan

    N Ozaki

  6. Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,

    H Ujike

  7. Okayama University, Okayama, Japan

    H Ujike

  8. Department of Psychiatry, Niigata University Graduate School of Medical and Denatal Sciences, Niigata, Japan

    T Muratake & T Someya

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  1. Y Horiuchi
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Correspondence to T Arinami.

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Horiuchi, Y., Ishiguro, H., Koga, M. et al. Support for association of the PPP3CC gene with schizophrenia. Mol Psychiatry 12, 891–893 (2007). https://doi.org/10.1038/sj.mp.4002019

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