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Association analysis of G-protein β3 subunit gene with altered Ca2+ homeostasis in bipolar disorder

Molecular Psychiatry volume 6, pages 125–126 (2001)Cite this article

SIR – Substantial evidence implicates disturbances in G-protein-mediated signal transduction and calcium (Ca2+) homeostasis in the pathophysiology of bipolar disorder (BD).123 We have previously demonstrated increased basal intracellular calcium concentration, [Ca2+]i, in B lymphoblast cell lines (BLCLs) from BD patients,4 which may be trait-dependent and reflect a putative endophenotype of BD. While the pathophysiological bases of the Ca2+ disturbances in BD remain largely unknown, abnormalities in Gq- and/or Gi-coupled phosphoinositide signaling could be involved.4 In addition to the noted alterations in the levels and function of Gαs and Gαq (reviewed in Li et al),2 altered Gαi mRNA abundance, immunolabeling and function have been observed in BD. Activation of PLC-β by released βγ from the Gαiβγ heterotrimer leads to inositol 1,4,5-trisphosphate (IP3) formation and subsequent release of Ca2+ from the endoplasmic reticulum (ER) storage pools.5 Thus, disturbances in Gi-mediated transduction mechanisms could affect the phosphoinositide and Ca2+ signaling systems in BD.

Of interest in this regard, a functional single nucleotide polymorphism (SNP) in the human G-protein β3 subunit gene (GNB3) is associated with an essential hypertensive (HT) phenotype of increased agonist-stimulated [Ca2+]i in BLCLs.6 A C→T transition (C825T) in exon 10 results in a shortened, more active, splice variant of the β3-subunit.6 This upregulated G-protein activity apparently leads to more efficient activation of PLC, increased IP3 formation, and Ca2+ release from ER stores that ultimately provokes cellular and vascular changes leading to HT.

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References

  1. Warsh JJ, Li PP . Curr Opin Psychiatry 1996 9: 23–29

  2. Li PP et al. In: Reith MEA (ed) Cerebral Signal Transduction: From First to Fourth Messengers Humana Press: Totowa, NJ 2000 283–309

    Chapter  Google Scholar 

  3. Warsh JJ, Li PP . In: Soares JC, Gershon S (eds) Bipolar Disorders: Basic Mechanisms and Therapeutic Implications Dekker: New York, NY 2000 201–226

    Google Scholar 

  4. Emamghoreishi M et al. Am J Psychiatry 1997 154: 976–982

  5. Camps M et al. Nature 1992 360: 684–686

    Article  CAS  Google Scholar 

  6. Siffert W et al. Nat Genet 1998 18: 45–48

    Article  CAS  Google Scholar 

  7. Detera-Wadleigh SD . Am J Med Genet 1999 88: 255–259

  8. Nielsen D et al. Am J Hum Genet 1999 63: 1531–1540

  9. Owen MJ et al. Mol Psychiatry 1997 2: 270–273

    Article  CAS  Google Scholar 

  10. Lander ES, Schork NJ . Science 1994 265: 2037–2048

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank W Hiscox, V Hoang and H Tims for subject management; A Kamble, D Sibony and M Green for laboratory assistance and C Spegg for statistical advice. This work was supported by a grant from MRC Canada (JJW) and an NSERC Scholarship (TWC).

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Authors and Affiliations

  1. Section of Biochemical Psychiatry, Centre for Addiction and Mental Health, Toronto, M5T 1R8, Ontario, Canada

    T W Corson, P P Li & J J Warsh

  2. Section of Neurogenetics, Centre for Addiction and Mental Health, Toronto, M5T 1R8, Ontario, Canada

    J L Kennedy & F Macciardi

  3. Mood Disorders Program, Centre for Addiction and Mental Health, Toronto, M5T 1R8, Ontario, Canada

    R G Cooke & S V Parikh

  4. Institute of Medical Science, University of Toronto, Canada

    T W Corson, J L Kennedy & J J Warsh

  5. Department of Pharmacology, University of Toronto, Canada

    P P Li & J J Warsh

  6. Department of Psychiatry, University of Toronto, Canada

    P P Li, J L Kennedy, F Macciardi, R G Cooke, S V Parikh & J J Warsh

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  1. T W Corson
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  2. P P Li
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  6. S V Parikh
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  7. J J Warsh
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Correspondence to J J Warsh.

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Corson, T., Li, P., Kennedy, J. et al. Association analysis of G-protein β3 subunit gene with altered Ca2+ homeostasis in bipolar disorder. Mol Psychiatry 6, 125–126 (2001). https://doi.org/10.1038/sj.mp.4000775

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