Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neuropsychopharmacology. 2009 Apr;34(5):1185-97. doi: 10.1038/npp.2008.187. Epub 2008 Oct 15.

A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain.

Author information

  • 1Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. yuferov@rockefeller.edu

Abstract

Dynorphin peptides and the kappa-opioid receptor are important in the rewarding properties of cocaine, heroin, and alcohol. We tested polymorphisms of the prodynorphin gene (PDYN) for association with cocaine dependence and cocaine/alcohol codependence. We genotyped six single nucleotide polymorphisms (SNPs), located in the promoter region, exon 4 coding, and 3' untranslated region, in 106 Caucasians and 204 African Americans who were cocaine dependent, cocaine/alcohol codependent, or controls. In Caucasians, we found point-wise significant associations of 3'UTR SNPs (rs910080, rs910079, and rs2235749) with cocaine dependence and cocaine/alcohol codependence. These SNPs are in high linkage disequilibrium, comprising a haplotype block. The haplotype CCT was significantly experiment-wise associated with cocaine dependence and with combined cocaine dependence and cocaine/alcohol codependence (false discovery rate, q=0.04 and 0.03, respectively). We investigated allele-specific gene expression of PDYN, using SNP rs910079 as a reporter, in postmortem human brains from eight heterozygous subjects, using SNaPshot assay. There was significantly lower expression for C allele (rs910079), with ratios ranging from 0.48 to 0.78, indicating lower expression of the CCT haplotype of PDYN in both the caudate and nucleus accumbens. Analysis of total PDYN expression in 43 postmortem brains also showed significantly lower levels of preprodynorphin mRNA in subjects having the risk CCT haplotype. This study provides evidence that a 3'UTR PDYN haplotype, implicated in vulnerability to develop cocaine addiction and/or cocaine/alcohol codependence, is related to lower mRNA expression of the PDYN gene in human dorsal and ventral striatum.

PMID:
18923396
[PubMed - indexed for MEDLINE]
PMCID:
PMC2778041
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk