Confirmation of the association between a polymorphism in the promoter region of the prodynorphin gene and cocaine dependence.
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.
Dahl
John P
JP
Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Clinical Research Building, Philadelphia, PA 19104, USA. jdahl@mail.med.upenn.edu
Weller
Andrew E
AE
Kampman
Kyle M
KM
Oslin
David W
DW
Lohoff
Falk W
FW
Ferraro
Thomas N
TN
O'Brien
Charles P
CP
Berrettini
Wade H
WH
D000328:Adult; D001741:Black or African American; D019970:Cocaine-Related Disorders / Q000208:ethnology / Q000235:genetics*; D004745:Enkephalins / Q000235:genetics* / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics* / Q000502:physiology
D004745:Enkephalins; D011498:Protein Precursors; C033660:preproenkephalin