Association of the κ-opioid system with alcohol dependence

X. Xuei, D. Dick, L. Flury-Wetherill, H. J. Tian, A. Agrawal, L. Bierut, A. Goate, K. Bucholz, M. Schuckit, J. Nurnberger, J. Tischfield, S. Kuperman, B. Porjesz, H. Begleiter, T. Foroud, H. J. Edenberg

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133 Scopus citations

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 κ-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the κ-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 κ-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 κ-opioid system.

Original languageEnglish (US)
Pages (from-to)1016-1024
Number of pages9
JournalMolecular Psychiatry
Volume11
Issue number11
DOIs
StatePublished - Nov 27 2006

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Keywords

  • κ-opioid receptor
  • Alcoholism
  • Dynorphin
  • Genetics
  • Opioids
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

Xuei, X., Dick, D., Flury-Wetherill, L., Tian, H. J., Agrawal, A., Bierut, L., Goate, A., Bucholz, K., Schuckit, M., Nurnberger, J., Tischfield, J., Kuperman, S., Porjesz, B., Begleiter, H., Foroud, T., & Edenberg, H. J. (2006). Association of the κ-opioid system with alcohol dependence. Molecular Psychiatry, 11(11), 1016-1024. https://doi.org/10.1038/sj.mp.4001882