Confirmation of the association between a polymorphism in the promoter region of the prodynorphin gene and cocaine dependence.

Abstract

The endogenous opioid system has been shown to have a role in the biological processes involved in addiction to numerous drugs of abuse including cocaine. It has recently been reported that the variable nucleotide tandem repeat (VNTR) polymorphism in the 5' promoter region of the prodynorphin gene, which encodes the precursor for three endogenous opioid peptides, is associated with the cocaine dependent phenotype. In order to confirm this finding, we genotyped the prodynorphin promoter polymorphism in cocaine dependent (n = 167) and control (n = 88) individuals of African descent. The results from this experiment indicate a statistically significant (chi2 = 5.64, OR = 1.59, P = 0.018) association between the prodynorphin promoter VNTR polymorphism and the cocaine dependent phenotype. In contrast to previous work showing increased risk conferred by one or two copies of the prodynorphin VNTR, the genotyping results from this study indicate that persons with three or four copies of this polymorphism are more likely to become cocaine dependent. This disparity suggests that the prodynorphin promoter VNTR may not be the functional polymorphism associating with the cocaine dependent phenotype. It is possible that different alleles of the prodynorphin promoter VNTR in the independent populations used for this and the previous study may be in linkage disequilibrium with a yet to be identified functional polymorphism in this gene.

• Authors: John P Dahl, Andrew E Weller, Kyle M Kampman, David W Oslin, Falk W Lohoff, Thomas N Ferraro, Charles P O'Brien, Wade H Berrettini
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 139B Issue 1 Pg. 106-8 (Nov 05 2005) ISSN: 1552-4841 [Print] United States
• PMID: 16184603 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2005 Wiley-Liss, Inc.

Chemical References

• Enkephalins
• Protein Precursors
• preproenkephalin

Topics

• Adult
• Black or African American
• Cocaine-Related Disorders (ethnology, genetics)
• Enkephalins (genetics, physiology)
• Female
• Genetic Predisposition to Disease
• Humans
• Male
• Polymorphism, Genetic
• Promoter Regions, Genetic
• Protein Precursors (genetics, physiology)