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  • Original Research Article
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An in-frame deletion in the α2C adrenergic receptor is common in African–Americans

Molecular Psychiatry volume 6, pages 168–172 (2001)Cite this article

Abstract

α2 adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The α2c adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6–25%) and an in-frame deletion of a homologous repeat at nucleotides 967–978 (ie, TIDRU1). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU2) and the deleted variant (TIDRU1) revealed that TIDRU1 had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African–American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU1 occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU1 with schizophrenia, additional studies are needed to see whether TIDRU1 confers a clinical phenotype.

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Acknowledgements

We thank Dr Jeffrey Longmate for power calculations, and Ms Nancy Gee and Ms Yasmin Valenzuela for skilled laboratory assistance. We thank Novartis for funds in partial support of the research.

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Authors and Affiliations

  1. Department of Molecular Genetics, City of Hope National Medical Center & Beckman Research Institute, 1500 East Duarte Road, Duarte, 91010, CA, USA

    J Feng, J Zheng, W P Bennett & S S Sommer

  2. Departments of Psychiatry, VA CT Healthcare System, and Yale University School of Medicine, West Haven, 06516, CT, USA

    J Gelernter

  3. Department of Psychiatry, University of Connecticut School of Medicine, Farmington, 06030, CT, USA

    H Kranzler

  4. Department of Psychiatry, University of Chicago, Chicago, 60611, IL, USA

    E Cook

  5. Laboratory of Neurogenetics, NIAAA, NIH, Rockville, 20852, MD, USA

    D Goldman

  6. Division of Neuroscience, University of Birmingham, Birmingham, B15 2QZ, UK

    I R Jones & N Craddock

  7. Department of Psychiatry, University of Washington, Seattle, 98195, WA, USA

    L L Heston

  8. Department of Psychiatry, SUNY-Stony Brook, Stony Brook, 11794, NY, USA

    L Delisi

  9. Dept of Human Genetics, UCLA School of Medicine, Los Angeles, 90095, CA, USA

    L Peltonen

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Correspondence to S S Sommer.

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Feng, J., Zheng, J., Gelernter, J. et al. An in-frame deletion in the α2C adrenergic receptor is common in African–Americans. Mol Psychiatry 6, 168–172 (2001). https://doi.org/10.1038/sj.mp.4000817

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  • DOI: https://doi.org/10.1038/sj.mp.4000817

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