The glycine transporter 1 gene (GLYT1) is associated with methamphetamine-use disorder

Authors

  • Yukitaka Morita,

    1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan
    Search for more papers by this author
  • Hiroshi Ujike,

    Corresponding author
    1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan
    2. Japanese Genetics Institute for Drug Abuse, Japan
    • Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
    Search for more papers by this author
  • Yuji Tanaka,

    1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan
    Search for more papers by this author
  • Makiko Kishimoto,

    1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan
    Search for more papers by this author
  • Yuko Okahisa,

    1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan
    Search for more papers by this author
  • Tatsuya Kotaka,

    1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan
    Search for more papers by this author
  • Mutsuo Harano,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Department of Neuropsychiatry, Kurume University Graduate School of Medicine, Kurume, Japan
    Search for more papers by this author
  • Toshiya Inada,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Department of Psychiatry, Teikyo University Ichikawa Hospital, Ichikawa, Japan
    Search for more papers by this author
  • Tokutaro Komiyama,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Division of Psychiatry, National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Japan
    Search for more papers by this author
  • Toru Hori,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Division of Psychiatry, National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Japan
    Search for more papers by this author
  • Mitsuhiko Yamada,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan
    Search for more papers by this author
  • Yoshimoto Sekine,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan
    Search for more papers by this author
  • Nakao Iwata,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Department of Psychiatry, Fujita Health University School of Medicine, Houmei, Japan
    Search for more papers by this author
  • Masaomi Iyo,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
    Search for more papers by this author
  • Ichiro Sora,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Division of Psychobiology, Department of Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan
    Search for more papers by this author
  • Norio Ozaki,

    1. Japanese Genetics Institute for Drug Abuse, Japan
    2. Department of Neuropsychiatry, Kurume University Graduate School of Medicine, Kurume, Japan
    Search for more papers by this author
  • Shigetoshi Kuroda

    1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama, Japan
    Search for more papers by this author

  • Please cite this article as follows: Morita Y, Ujike H, Tanaka Y, Kishimoto M, Okahisa Y, Kotaka T, Harano M, Inada T, Komiyama T, Hori T, Yamada M, Sekine Y, Iwata N, Iyo M, Sora I, Ozaki N, Kuroda S. 2007. The Glycine Transporter 1 Gene (GLYT1) is Associated With Methamphetamine-Use Disorder. Am J Med Genet Part B 147B:54–58.

Abstract

Glycine transporter (GlyT)-1 plays a pivotal role in maintaining the glycine level at the glutamatergic synapse. Glycine is an allosteric agonist of N-methyl-D-aspartate (NMDA) receptors. Because activation of NMDA receptors is an essential step for induction of methamphetamine dependence and psychosis, differences in the functioning of GlyT-1 due to genetic variants of the GlyT-1 gene (GLYT1) may influence susceptibility. A case-control genetic association study of the GLYT1 gene examined 204 patients with methamphetamine-use disorder and 210 healthy controls. We examined three single nucleotide polymorphisms (SNPs), SNP1, IVS3 + 411C > T, rs2486001; SNP2, 1056G > A, rs2248829; and SNP3, IVS11 + 22G > A, rs2248632, of the GLYT1 gene and found that SNP1 showed a significant association in both genotype (P = 0.0086) and allele (P = 0.0019) with methamphetamine-use disorder. The T-G haplotype at SNP1 and SNP2 was a significant risk factor for the disorder (P = 0.000039, odds ratio: 2.04). The present findings indicate that genetic variation of the GLYT1 gene may contribute to individual vulnerability to methamphetamine dependence and psychosis. © 2007 Wiley-Liss, Inc.

Ancillary