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Variation within voltage-gated calcium channel genes and antipsychotic treatment response in a South African first episode schizophrenia cohort

The Pharmacogenomics Journal volume 19, pages 109–114 (2019)Cite this article

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Abstract

Voltage-gated calcium channels have been implicated in schizophrenia aetiology; however, little is known about their involvement in antipsychotic treatment response. This study investigated variants within the calcium channel subunit genes for association with antipsychotic treatment response in a first episode schizophrenia cohort. Twelve regulatory variants within seven genes were shown to be significantly associated with treatment outcome. Most notably, the CACNA1B rs2229949 CC genotype was associated with improved negative symptomology, where the C allele was predicted to abolish a miRNA-binding site (has-mir-5002-3p), suggesting a possible mechanism of action through which this variant may have an effect. These results implicate the calcium channel subunits in antipsychotic treatment response and suggest that increased activation of these channels may be explored to enhance or predict antipsychotic treatment outcome.

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Acknowledgements

The work reported here was supported by the following grants provided by the South African National Research Foundation (NRF), i.e., KSO'C was funded by the Scarce Skills Post-Doctoral Fellowship (grant no. 96833) and LW was funded by the Competitive Program for Rated Researchers (grant no. 93498) and the Bioinformatics and Functional Genomics Program (grant no. 93681). The opinions expressed and conclusions arrived at are those of the authors and are not necessarily attributed to these funding sources.

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Authors and Affiliations

  1. System Genetics Working Group, Department of Genetics, Faculty of AgriSciences, Stellenbosch University, Stellenbosch, South Africa

    Kevin S. O’Connell & Nathaniel W. McGregor

  2. Department of Genetics, Faculty of AgriSciences, Stellenbosch University, Stellenbosch, South Africa

    Kevin S. O’Connell, Nathaniel W. McGregor & Louise Warnich

  3. Department of Psychiatry, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, New York, NY, USA

    Anil Malhotra & Todd Lencz

  4. Department of Psychiatry, Faculty of Medicine and Health Sciences, Tygerberg Medical Campus, Tygerberg, Stellenbosch University, Stellenbosch, South Africa

    Robin Emsley

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  1. Kevin S. O’Connell
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Correspondence to Louise Warnich.

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O’Connell, K.S., McGregor, N.W., Malhotra, A. et al. Variation within voltage-gated calcium channel genes and antipsychotic treatment response in a South African first episode schizophrenia cohort. Pharmacogenomics J 19, 109–114 (2019). https://doi.org/10.1038/s41397-018-0033-5

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