Association analysis of genes encoding the nociceptin receptor (OPRL1) and its endogenous ligand (PNOC) with alcohol or illicit drug dependence

Xiaoling Xuei, Leah Flury-Wetherill, Laura Almasy, Laura Bierut, Jay Tischfield, Marc Schuckit, John I. Nurnberger, Tatiana Foroud, Howard J. Edenberg

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Recent studies in animal models have shown that the nociceptin system, comprising nociceptin (or OFQ/N, encoded by PNOC) and the nociceptin receptor (an opioid receptor-like protein encoded by OPRL1), may be involved in alcohol and other drug reward pathways. To determine whether the nociceptin system is associated with alcohol or illicit drug dependence in humans, we analyzed 10 single nucleotide polymorphisms (SNPs) in OPRL1 and 15 SNPs in PNOC in a sample of 1923 European Americans from 219 multiplex alcohol dependent families ascertained by the Collaborative Study on the Genetics of Alcoholism. The SNPs spanned both genes and several kb of their flanking sequences, and were in high linkage disequilibrium. Neither gene was associated with alcohol or illicit drug dependence, although two SNPs in PNOC showed marginal association with alcoholism and one with illicit drug dependence (P = 0.04-0.05). Secondary analyses suggested that two adjacent SNPs in intron 1 of OPRL1 were marginally associated with opioid dependence (P = 0.05); none of the SNPs in PNOC were associated with opioid dependence.

Original languageEnglish (US)
Pages (from-to)80-87
Number of pages8
JournalAddiction Biology
Volume13
Issue number1
DOIs
StatePublished - Mar 2008

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Keywords

  • Alcoholism
  • Association
  • Drug dependence
  • Nociceptin system
  • Opioid
  • Polymorphism

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