The Dopamine Receptor D2 (DRD2) SNP rs1076560 is Associated with Opioid Addiction

Authors

  • Toni-Kim Clarke,

    Corresponding author
    1. Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    • Corresponding author: Toni-Kim Clarke, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, UK. Tel: 215 898 4203; Fax: 0131 537 6291; E-mail: Toni.Clarke@ed.ac.uk

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  • Amy R. D. Weiss,

    1. Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Thomas N. Ferarro,

    1. Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Kyle M. Kampman,

    1. Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Charles A. Dackis,

    1. Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Helen M. Pettinati,

    1. Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Charles P. O'brien,

    1. Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • David W. Oslin,

    1. Treatment Research Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    2. VA Medical Center, Philadelphia, PA, USA
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  • Falk W. Lohoff,

    1. Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Wade H. Berrettini

    1. Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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Summary

The risk for drug addiction is partially heritable. Genes of the dopamine system are likely candidates to harbour risk variants, as dopamine neurotransmission is involved in mediating the rewarding effects of drugs of abuse. One functional single nucleotide polymorphism in dopamine receptor D2 (DRD2), rs1076560, is involved in regulating splicing of the gene and alters the ratio of DRD2 isoforms located pre- and postsynaptically. rs1076560 has been previously associated with cocaine abuse and we set out to confirm this association in a sample of European American (EA) (n = 336) and African American (AA) (n = 1034) cocaine addicts and EA (n = 656) and AA (n = 668) controls. We also analysed the role of rs1076560 in opioid dependence by genotyping EA (n = 1041) and AA (n = 284) opioid addicts. rs1076560 was found to be nominally associated with opioid dependence in EAs (p = 0.02, OR = 1.27) and AAs (p = 0.03, OR = 1.43). When both opioid-addicted ancestral samples were combined, rs1076560 was significantly associated with increased risk for drug dependence (p = 0.0038, OR = 1.29). This association remained significant after correction for multiple testing. No association was found with cocaine dependence. These data demonstrate the importance of dopamine gene variants in the risk for opioid dependence and highlight a functional polymorphism that warrants further study.

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