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Polymorphisms in the dopamine transporter gene (SLC6A3/DAT1) and alcohol dependence in humans: a systematic review

    Carmen S van der Zwaluw

    † Author for correspondence

    Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands.

    ,
    Rutger CME Engels

    Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands.

    ,
    Jan Buitelaar

    Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands.

    ,
    Robbert J Verkes

    Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands.

    ,
    Barbara Franke

    Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands.

    &
    Ron HJ Scholte

    Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands.

    Published Online:https://doi.org/10.2217/pgs.09.24

    Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic neurotransmission, making the gene encoding the transporter (SLC6A3/DAT1) an attractive candidate in clinical studies on alcohol dependence. We conducted a systematic review of 18 studies examining associations between polymorphisms in DAT1 and alcohol dependence. The DAT1 variable number tandem repeat, the most frequent studied polymorphism in DAT1, did not show a direct association with alcohol dependence in general. Several, but not all, studies found that the DAT1 variable number tandem repeat (9-repeat allele) was associated with alcohol-withdrawal symptoms, such as seizures and delirium tremens. We discuss shortcomings, such as lack of power and disregarding moderating variables, as well as future challenges of gene association studies.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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