Response to methylphenidate in adults with ADHD is associated with a polymorphism in SLC6A3 (DAT1)

Authors

  • J. Sandra Kooij,

    Corresponding author
    1. PsyQ, Psycho-Medical Programs, The Hague, The Netherlands
    • PsyQ, Psycho-Medical Programs, Program Adult ADHD, Carel Reinierskade 197, 2593 HR Den Haag, The Netherlands.
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    • J. Sandra Kooij has been a consultant to/member of advisory board of/and/or speaker for Janssen Cilag BV and Eli Lilly.

  • A. Marije Boonstra,

    1. Department of Psychology, Erasmus University Rotterdam, The Netherlands
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  • Sita H. Vermeulen,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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  • Angelien G. Heister,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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  • Huibert Burger,

    1. Department of Psychiatry and Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands
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  • Jan K. Buitelaar,

    1. Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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    • Jan K. Buitelaar has been a consultant to/member of advisory board of/and/or speaker for Janssen Cilag BV, Eli Lilly, Bristol-Myer Squibb, UBC, Shire, Medice.

  • Barbara Franke

    1. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    2. Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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  • Please cite this article as follows: Kooij JS, Boonstra AM, Vermeulen SH, Heister AG, Burger H, Buitelaar JK, Franke B. 2008. Response to Methylphenidate in Adults With ADHD is Associated With a Polymorphism in SLC6A3 (DAT1). Am J Med Genet Part B 147B:201–208.

Abstract

In this pharmacogenetic study in adults with ADHD (n = 42), a stratified analysis was performed of the association between response to methylphenidate (MPH), assessed under double-blind conditions, and polymorphisms in the genes encoding the dopamine transporter, SLC6A3 (DAT1), the norepinephrine transporter, SLC6A2 (NET), and the dopamine receptor D4, DRD4. The VNTR polymorphism in the 3′ untranslated region of SLC6A3 was significantly associated with an increased likelihood of a response to MPH treatment (OR 3.8; 95% CI 1.0–15.2, and OR 5.4; 95% CI 1.4–21.9, depending on the definition of response) in carriers of a single 10-repeat allele compared to patients with the 10/10 genotype. The polymorphisms in DRD4 and the SLC6A2 were not associated with treatment response. This study supports a role of the SLC6A3 genotype in determining the response to MPH in the treatment of adults with ADHD. © 2007 Wiley-Liss, Inc.

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