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No association of alcohol dependence with a NMDA-receptor 2B gene variant

Molecular Psychiatry volume 8, pages 11–12 (2003)Cite this article

SIR – Alcohol dependence is a disorder with strong genetic influences and heritability estimates ranging between 40 and 60%.1 Recent results have demonstrated the importance of ethanol-induced glutamatergic neurotransmission for the development of alcohol dependence. Ethanol-induced glutamatergic neurotransmission has been shown to influence pathophysiological mechanisms central to the development of alcohol dependence, including tolerance, withdrawal symptoms, craving and ethanol-related neurotoxicity.2 We performed an association study of alcohol dependence and a silent single nucleotide polymorphism (SNP) of the N-methyl-D-aspartate (NMDA) receptor 2B (NR2B) subunit leading to a C to T exchange at position 2873 of the gene (accession number XM 006636.2).3 A total of 204 patients (157 males, 47 females) with alcohol dependence according to DSM-IV criteria and 258 unrelated control subjects (138 males, 120 females) were included in the study.

Ethanol acts specifically by inhibiting NMDA receptors. It inhibits NMDA evoked release of various neurotransmitters.4 In case of acute withdrawal from ethanol, increased expression of NMDA receptors results in a heightened excitability, which is thought to contribute to clinical symptoms such as seizures, delirium tremens and neuronal cell death leading to brain atrophy.5 NR2B and NR2A are subunits that confer a high sensitivity to ethanol-induced inhibition.6 Ethanol withdrawal signs in mice have been suppressed by treatment with the selective NR2B-containing NMDA receptor antagonist, ifenprodil.7 In addition, the pharmacological action of the anticraving drug acamprosate is thought to be mediated by its interaction with a polyamine site particularly on the NMDA-receptor 2B subunit.8 These findings suggest a direct, but not exclusive, involvement of the NR2B subunit in alcohol dependence. The goal of the present study was to analyse if an association of alcohol dependence with the NR2B polymorphism can be detected.

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Authors and Affiliations

  1. Department of Psychiatry, Central Institute of Mental Health (CIMH), Mannheim, Germany

    G Schumann & F A Henn

  2. Department of Psychiatry and Psychotherapy, Molecular Neurobiology, University of Munich, Germany

    D Rujescu & I Giegling

  3. Department of Psychiatry and Psychotherapy, University of Mainz, Germany

    A Szegedi, P Singer, C Klawe & N Dahmen

  4. Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany

    S Wiemann

  5. Department of Biostatistics, CIMH, Mannheim

    S Wellek

  6. Department of Psychiatry, Benjamin-Franklin Hospital, Free University, Berlin

    I Anghelescu

  7. Department of Psychiatry, Charité, Humboldt University, Berlin

    A Heinz

  8. Department of Psychopharmacology CIMH, Mannheim

    R Spanagel

  9. Department of Addictive Behaviour and Addiction Medicine, CIMH, Mannheim, Germany

    K Mann

Authors
  1. G Schumann
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  2. D Rujescu
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  3. A Szegedi
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  4. P Singer
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  5. S Wiemann
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  6. S Wellek
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  7. I Giegling
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  8. C Klawe
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  9. I Anghelescu
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  10. A Heinz
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  11. R Spanagel
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  12. K Mann
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  13. F A Henn
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  14. N Dahmen
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Correspondence to G Schumann.

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Schumann, G., Rujescu, D., Szegedi, A. et al. No association of alcohol dependence with a NMDA-receptor 2B gene variant. Mol Psychiatry 8, 11–12 (2003). https://doi.org/10.1038/sj.mp.4001245

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  • DOI: https://doi.org/10.1038/sj.mp.4001245

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