Association of the kappa-opioid system with alcohol dependence

Mol Psychiatry. 2006 Nov;11(11):1016-24. doi: 10.1038/sj.mp.4001882. Epub 2006 Aug 22.

Abstract

Opioid receptors and their endogenous peptide ligands play important roles in the reward and reinforcement of drugs such as heroin, cocaine, and alcohol. The binding of dynorphins to the kappa-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the kappa-opioid receptor, and PDYN, which encodes its ligand prodynorphin, in a group of 1860 European American individuals from 219 multiplex alcohol dependent families. Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in the promoter and 3' end of PDYN, and in intron 2 of OPRK1. Haplotype analyses further supported the association of PDYN. Thus, variations in the genes encoding both the kappa-opioid receptor and its ligand, OPRK1 and PDYN, are associated with the risk for alcohol dependence; this makes biological sense as variations in either should affect signaling through the kappa-opioid system.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / genetics*
  • Alcoholism / metabolism
  • Enkephalins / genetics*
  • Enkephalins / metabolism
  • European Continental Ancestry Group / genetics
  • Genetic Predisposition to Disease
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics*
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism
  • Receptors, Opioid, kappa / genetics*
  • Receptors, Opioid, kappa / metabolism
  • Risk Factors

Substances

  • Enkephalins
  • OPRK1 protein, human
  • Protein Precursors
  • Receptors, Opioid, kappa
  • kappa(1) opioid receptor
  • preproenkephalin