Throwing the Micro Switch: microRNA May Link Smoking Risk Gene to Neurobiology of Addiction

Philadelphia, PA, April 23, 2009 – During the past several years, significant progress has been made in identifying susceptibility genes for nicotine dependence through genetic linkage and association analyses. Although a large number of genes have been associated with tobacco smoking, only a very limited number of genetic variants are considered to be causative. How to find these functional variants and then characterize them remains challenging in the field of human genetics.

In the traditional genetic dogma, DNA codes for RNA and RNA codes for protein. But what about the leftover bits of RNA that do not seem to code for proteins? One type of RNA ‘leftovers’ is the microRNAs. These small pieces of RNA do not code for proteins. Instead, they influence the extent to which other genes are expressed, i.e., the rate or extent of conversion of DNA to RNA. To date, there have been relatively few examples of the direct involvement of microRNAs in psychiatric disorders.

However, a study scheduled for publication in the April 15th issue of Biological Psychiatry, published by Elsevier, has now provided new insights into how variation in the dopamine D1 receptor gene (DRD1) may be linked to the risk for nicotine dependence through microRNA action.

Huang and Li, researchers at the University of Virginia, previously showed that the DRD1 gene, one of the major receptors in the brain that mediate the actions of the neurotransmitter dopamine, is associated with tobacco dependence, and that two alleles of a variant within this gene are differentially expressed. “In the current study, we demonstrated that such differential expression of DRD1 is regulated by microRNA miR-504,” explains Dr. Li.

In other words, this microRNA seems to directly influence how these genetic variations are expressed within the DRD1 gene, thereby influencing ones risk to developing nicotine dependence. John Krystal, M.D., Editor of Biological Psychiatry, comments: “This study provides an interesting example of how variation in a gene that contributes to the risk of smoking may do so by throwing a ‘micro switch’ and thereby increasing the expression of the dopamine 1 receptor gene.”

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Notes to Editors:
The article is “Differential Allelic Expression of Dopamine D1 Receptor Gene (DRD1) Is Modulated by microRNA miR-504” by Weihua Huang and Ming D. Li. The authors are affiliated with the Departments of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia. The article appears in Biological Psychiatry, Volume 65, Issue 8 (April 15, 2009), published by Elsevier. The authors’ disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D. is affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System and his disclosures of financial and conflicts of interests are available here.

Full text of the article mentioned above is available upon request. Contact Jayne M. Dawkins at ja.dawkins@elsevier.com to obtain a copy or to schedule an interview.

About Biological Psychiatry
This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

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Media Contact:
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