The opioid system in alcohol and drug dependence

Family-based association study

Xiaoling Xuei, Leah Flury-Wetherill, Laura Bierut, Danielle Dick, John Nurnberger, Tatiana Foroud, Howard Edenberg

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Opioid receptors and their endogenous peptide ligands play important roles in neurotransmission and neuromodulation in response to addictive drugs such as heroin, cocaine, and alcohol. In an earlier study, we reported that variation in the genes encoding the κ-opioid receptor (OPRK1) and its peptide ligand (PDYN) were associated with the risk for alcoholism. We continued our investigation of the role of the opioid system in alcohol dependence by analyzing the genes encoding the μ- and δ-opioid receptors and their peptide ligands. We analyzed 18 OPRM1 SNPs, 18 OPRD1 SNPs, 7 PENK SNPs, and 7 POMC SNPs in a sample of 1923 European Americans from 219 multiplex alcohol dependent families. Employing a family-based test of association, we found no evidence that these four genes were significantly associated with alcohol dependence. We also did not find association between these genes and illicit drug dependence. Secondary analyses employing the narrower phenotype of opioid dependence (83 affected individuals) demonstrated association with SNPs in PENK and POMC, but not in OPRM1 or OPRD1. Haplotype analyses provided further support for the association of PENK and POMC with opioid dependence. Therefore, our data provide no support for the idea that variations in OPRM1, OPRD1, PENK and POMC are associated with alcohol dependence or general illicit drug dependence, but variations in PENK and POMC appear to be associated with the narrower phenotype of opioid dependence in these families.

Original languageEnglish
Pages (from-to)877-884
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume144
Issue number7
DOIs
StatePublished - Oct 5 2007

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Pro-Opiomelanocortin
Opioid Analgesics
Alcoholism
Substance-Related Disorders
Single Nucleotide Polymorphism
Opioid Receptors
Street Drugs
Ligands
Peptides
Genes
Alcohols
Phenotype
Heroin
Cocaine
Synaptic Transmission
Haplotypes
Pharmaceutical Preparations

Keywords

  • μ- and δ-opioid receptors
  • Alcoholism
  • Endorphins
  • Enkephalins
  • Genetics

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

The opioid system in alcohol and drug dependence : Family-based association study. / Xuei, Xiaoling; Flury-Wetherill, Leah; Bierut, Laura; Dick, Danielle; Nurnberger, John; Foroud, Tatiana; Edenberg, Howard.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 144, No. 7, 05.10.2007, p. 877-884.

Research output: Contribution to journalArticle

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