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An in-frame deletion in the alpha2C adrenergic receptor is common in African-Americans

Feng, J., Zheng, J., Gelernter, J., Kranzler, H., Cook, E., Goldman, D., Jones, Ian Richard ORCID:, Craddock, Nicholas John ORCID:, Heston, L. L., Delisi, L., Peltonen, L., Bennett, W. P. and Sommer, S. S. 2001. An in-frame deletion in the alpha2C adrenergic receptor is common in African-Americans. Molecular Psychiatry 6 (2) , pp. 168-172. 10.1038/

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Alpha 2 adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The 2c 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: adrenergic receptor; schizophrenia; genetic polymorphism; case-control series; gene deletion; behavior disorder
Publisher: Nature Publishing Group
ISSN: 1359-4184
Last Modified: 27 Oct 2022 08:24

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