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Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain

Authors

  • Eva J. Brandl,

    1. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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  • Arun K. Tiwari,

    1. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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  • Tristram A. Lett,

    1. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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  • Sajid A. Shaikh,

    1. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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  • Jeffrey A. Lieberman,

    1. Department of Psychiatry, College of Physicians and Surgeons, Columbia University and the New York State Psychiatric Institute, New York, NY, USA
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  • Herbert Y. Meltzer,

    1. Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
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  • James L. Kennedy,

    1. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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  • Daniel J. Müller

    Corresponding author
    • Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada
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Correspondence to: D. J. Müller, Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Tel: + 1 416 535 8501 ext 6851; Fax: +1 416 979 4666. E-mail: daniel.mueller@camh.ca

Abstract

Background

Previous studies have shown that antipsychotics with high propensity for antipsychotic-induced weight gain (AIWG) influence glucose transporter type 4 (GLUT4) mediated glucose intake. Variation in the gene encoding TBC1 domain family member 1 (TBC1D1), a Rab-GTPase activating protein regulating GLUT4 trafficking, has been associated with obesity. Therefore, we investigated the impact of TBC1D1 polymorphisms on AIWG.

Methods

We analyzed rs9852 and rs35859249 in TBC1D1 in 195 schizophrenia subjects treated mostly with clozapine or olanzapine for up to 14 weeks. Association was tested using analysis of variance and analysis of covariance with change (%) from baseline weight as the dependent variable.

Results

Analysis of covariance showed a non-significant trend for lower weight gain in carriers of the T-allele of rs9852 than in C-allele homozygotes (p = 0.063). This effect was more pronounced in the subgroup of patients treated with clozapine or olanzapine (p = 0.024). For rs35859249, no significant association with AIWG could be detected.

Conclusions

This is the first study examining the association between TBC1D1 and AIWG. The moderate association of rs9852, located in the 3′UTR near a miRNA binding site, indicates an influence of TBC1D1 on AIWG. Further investigations remain necessary to elucidate the role of this gene in AIWG. Copyright © 2013 John Wiley & Sons, Ltd.

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