Skip to main content
Log in

No association with the calcineurin A gamma subunit gene (PPP3CC) haplotype to Japanese schizophrenia

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

Calcineurin, one of the serine/threonine protein phosphatase, comprises more than 1% of the total protein content in brain. This evidence points towards important roles of calcineurin in neural function. Miyakawa et al. reported that forebrain-specific calcineurin knockout mice showed the behavioral abnormalities that are often observed in schizophrenia patients. Based on this evidence, they suggested that calcineurin dysfunction could be involved in schizophrenia pathogenesis. Thereafter this report, Gerber et al. performed transmission disequilibrium test (TDT) studies and showed an evidence for a nominally significant over-transmission of a common haplotype of the human calcineurin A γ subunit gene (PPP3CC). We performed association analysis of PPP3CC in Japanese sample of 457 schizophrenia cases and 429 controls. To our regret, we could not confirm the association with Japanese schizophrenia to PPP3CC including core at-risk haplotype. Our result suggests that PPP3CC may not play a major role in Japanese schizophrenia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • JL Blouin et al. (1998) ArticleTitleSchizophrenia susceptibility loci on chromosomes 13q32 and 8p2. Nat Genet 20 IssueID1 70–73 Occurrence Handle10.1038/1734 Occurrence Handle9731535

    Article  PubMed  Google Scholar 

  • D Fallin NJ Schork (2000) ArticleTitleAccuracy of haplotype frequency estimation for biallelic loci, via the expectation–maximization algorithm for unphased diploid genotype data. Am J Hum Genet 67 IssueID4 947–959 Occurrence Handle10.1086/303069 Occurrence Handle10954684

    Article  PubMed  Google Scholar 

  • DJ Gerber et al. (2003) ArticleTitleEvidence for association of schizophrenia with genetic variation in the 8p213 gene, PPP3CC, encoding the calcineurin gamma subunit. Proc Natl Acad Sci USA 100 IssueID15 8993–8998 Occurrence Handle10.1073/pnas.1432927100 Occurrence Handle12851458

    Article  PubMed  Google Scholar 

  • LA Glantz DA Lewis (2001) ArticleTitleDendritic spine density in schizophrenia and depression. Arch Gen Psychiatry 58 IssueID2 203 Occurrence Handle10.1001/archpsyc.58.2.203

    Article  Google Scholar 

  • IA Graef et al. (2003) ArticleTitleNeurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Cell 113 IssueID5 657–670 Occurrence Handle10.1016/S0092-8674(03)00390-8 Occurrence Handle12787506

    Article  PubMed  Google Scholar 

  • P Greengard (2001) ArticleTitleThe neurobiology of slow synaptic transmission. Science 294 IssueID5544 1024–1030 Occurrence Handle10.1126/science.294.5544.1024 Occurrence Handle11691979

    Article  PubMed  Google Scholar 

  • D Guerini et al. (1990) ArticleTitleMultiple forms of calcineurin, a brain isozyme of the calmodulin-stimulated protein phosphatase. Adv Second Messenger Phosphoprotein Res 24 242–247 Occurrence Handle2169804

    PubMed  Google Scholar 

  • HM Gurling et al. (2001) ArticleTitleGenomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q322, 5q332, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q233-24 and 20q121-1123. Am J Hum Genet 68 IssueID3 661–673 Occurrence Handle10.1086/318788 Occurrence Handle11179014

    Article  PubMed  Google Scholar 

  • JSSLG (2003) Initial genome-wide scan for linkage with schizophrenia in the Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) families. Am J Med Genet 120B(1): 22–28

    Google Scholar 

  • KS Kendler et al. (1996) ArticleTitleEvidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families. Am J Psychiatry 153 IssueID12 1534–1540 Occurrence Handle8942448

    PubMed  Google Scholar 

  • MS Keshavan (1999) ArticleTitleDevelopment, disease and degeneration in schizophrenia: a unitary pathophysiological model. J Psychiatr Res 33 IssueID6 513–521 Occurrence Handle10.1016/S0022-3956(99)00033-3 Occurrence Handle10628528

    Article  PubMed  Google Scholar 

  • CB Klee H Ren X Wang (1998) ArticleTitleRegulation of the calmodulin-stimulated protein phosphatase, calcineurin. J Biol Chem 273 IssueID22 13367–13370 Occurrence Handle10.1074/jbc.273.22.13367 Occurrence Handle9593662

    Article  PubMed  Google Scholar 

  • DN Lieberman I Mody (1994) ArticleTitleRegulation of NMDA channel function by endogenous Ca(2+)-dependent phosphatase. Nature 369 IssueID6477 235–239 Occurrence Handle10.1038/369235a0 Occurrence Handle7514273

    Article  PubMed  Google Scholar 

  • JS Liu et al. (2001) ArticleTitleBayesian analysis of haplotypes for linkage disequilibrium mapping. Genome Res 11 IssueID10 1716–1724 Occurrence Handle10.1101/gr.194801 Occurrence Handle11591648

    Article  PubMed  Google Scholar 

  • T Miyakawa et al. (2003) ArticleTitleConditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci USA 100 IssueID15 8987–8992 Occurrence Handle10.1073/pnas.1432926100 Occurrence Handle12851457

    Article  PubMed  Google Scholar 

  • B Moghaddam (2003) ArticleTitleBringing order to the glutamate chaos in schizophrenia. Neuron 40 IssueID5 881–884 Occurrence Handle10.1016/S0896-6273(03)00757-8 Occurrence Handle14659087

    Article  PubMed  Google Scholar 

  • RA Nichols GR Suplick JM Brown (1994) ArticleTitleCalcineurin-mediated protein dephosphorylation in brain nerve terminals regulates the release of glutamate. J Biol Chem 269 IssueID38 23817–23823 Occurrence Handle7522234

    PubMed  Google Scholar 

  • J Ohashi et al. (2001) ArticleTitleComparison of statistical power between 2 * 2 allele frequency and allele positivity tables in case-control studies of complex disease genes. Ann Hum Genet 65 IssueIDPt 2 197–206 Occurrence Handle10.1017/S000348000100851X Occurrence Handle11434330

    Article  PubMed  Google Scholar 

  • AE Pulver et al. (1995) ArticleTitleSchizophrenia: a genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes. Am J Med Genet 60 IssueID3 252–260 Occurrence Handle10.1002/ajmg.1320600316 Occurrence Handle7573181

    Article  PubMed  Google Scholar 

  • F Shibasaki U Hallin H Uchino (2002) ArticleTitleCalcineurin as a multifunctional regulator. J Biochem (Tokyo) 131 IssueID1 1–15

    Google Scholar 

  • RE Straub et al. (2002) ArticleTitleGenome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes. Mol Psychiatry 7 IssueID6 542–559 Occurrence Handle10.1038/sj.mp.4001051 Occurrence Handle12140777

    Article  PubMed  Google Scholar 

  • T Suzuki et al. (2003) ArticleTitleAssociation of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia. Am J Med Genet 121B IssueID1 7–13 Occurrence Handle10.1002/ajmg.b.20060

    Article  Google Scholar 

  • G Tong D Shepherd CE Jahr (1995) ArticleTitleSynaptic desensitization of NMDA receptors by calcineurin. Science 267 IssueID5203 1510–1512 Occurrence Handle7878472

    PubMed  Google Scholar 

  • RW Wallace EA Tallant WY Cheung (1980) ArticleTitleHigh levels of a heat-labile calmodulin-binding protein (CaM-BP80) in bovine neostriatum. Biochemistry 19 IssueID9 1831–1837 Occurrence Handle10.1021/bi00550a016 Occurrence Handle6246935

    Article  PubMed  Google Scholar 

  • A Wassef J Baker LD Kochan (2003) ArticleTitleGABA and schizophrenia: a review of basic science and clinical studies. J Clin Psychopharmacol 23 IssueID6 601–640 Occurrence Handle10.1097/01.jcp.0000095349.32154.a5 Occurrence Handle14624191

    Article  PubMed  Google Scholar 

  • DR Weinberger (1999) ArticleTitleCell biology of the hippocampal formation in schizophrenia. Biol Psychiatry 45 IssueID4 395–402 Occurrence Handle10.1016/S0006-3223(98)00331-X Occurrence Handle10071707

    Article  PubMed  Google Scholar 

  • JL Yakel (1997) ArticleTitleCalcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription. Trends Pharmacol Sci 18 IssueID4 124–134 Occurrence Handle10.1016/S0165-6147(97)01046-8 Occurrence Handle9149541

    Article  PubMed  Google Scholar 

  • K Yamada et al. (2004) ArticleTitleFamily-based association study of schizophrenia with 444 markers and analysis of a new susceptibility locus mapped to 11q133. Am J Med Genet 127B IssueID1 11–19 Occurrence Handle10.1002/ajmg.b.20166

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kinoshita, Y., Suzuki, T., Ikeda, M. et al. No association with the calcineurin A gamma subunit gene (PPP3CC) haplotype to Japanese schizophrenia. J Neural Transm 112, 1255–1262 (2005). https://doi.org/10.1007/s00702-004-0261-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-004-0261-5

Navigation