Advertisement

Mu Opioid Receptor Genetic Variation and Heroin Addiction

  • Jon-Kar Zubieta
    Correspondence
    Address correspondence to Jon-Kar Zubieta, M.D., Ph.D., Department of Psychiatry, University of Utah Health Science Center, University of Utah, 501 Chipeta Way, Salt Lake City, UT 84108
    Affiliations
    Department of Psychiatry and University Neuropsychiatry Institute, University of Utah Health Science Center, University of Utah, Salt Lake City, Utah
    Search for articles by this author
      The article by Hancock et al. (
      • Hancock D.B.
      • Levy J.L.
      • Gaddis N.C.
      • Glasheen C.
      • Saccone N.L.
      • Page G.P.
      • et al.
      Cis-Expression quantitative trait loci mapping reveals replicable associations with heroin addiction in OPRM1.
      ) examines the functional significance of single nucleotide polymorphisms (SNPs) in the mu opioid receptor (OPRM1) gene as it pertains to associations with heroin addiction. In this work, cis-expression quantitative trait analyses in control, nonaddicted postmortem samples (BrainCloud participants) were employed to reduce an initial sample of 103 SNPs to 16 that were found to be associated with changes in messenger RNA expression and presented functional significance. The 16 SNPs were tested for association with heroin addiction using blood samples from participants in the Urban Health Study. Control data were acquired using six cohorts from the Database of Genotypes and Phenotypes. Final samples included 2004 subjects with heroin addiction and 8753 population control subjects; both samples comprised European Americans and African Americans. Four common functional SNPs, rs9478495, rs3778150, rs9384169, and rs562859, with a range of allelic frequencies of 16%–38%, were significantly associated with heroin addiction. A replication study employing samples from the Alcohol Dependence GWAS in European- and African Americans study and Australian data sets comprised 2828 subjects with heroin/other opioid addiction and 3689 control subjects. Among the SNPs initially significantly associated, rs3778150, with its C allele showing lower OPRM1 expression in the BrainCloud sample, was replicated in the second cohort.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hancock D.B.
        • Levy J.L.
        • Gaddis N.C.
        • Glasheen C.
        • Saccone N.L.
        • Page G.P.
        • et al.
        Cis-Expression quantitative trait loci mapping reveals replicable associations with heroin addiction in OPRM1.
        Biol Psychiatry. 2015; 78: 474-484
        • Zhang Y.
        • Wang D.
        • Johnson A.D.
        • Papp A.C.
        • Sadee W.
        Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G.
        J Biol Chem. 2005; 280: 32618-32624
        • Pecina M.
        • Love T.
        • Stohler C.S.
        • Goldman D.
        • Zubieta J.K.
        Effects of the Mu opioid receptor polymorphism (OPRM1 A118G) on pain regulation, placebo effects and associated personality trait measures.
        Neuropsychopharmacology. 2015; 40: 957-965
        • Zubieta J.K.
        • Smith Y.R.
        • Bueller J.M.
        • Xu Y.
        • Kilbourn M.R.
        • Meyer C.R.
        • et al.
        Regional mu opioid receptor regulation of sensory and affective dimensions of pain.
        Science. 2001; 293: 311-315
        • Panksepp J.
        • Herman B.H.
        • Vilberg T.
        • Bishop P.
        • DeEskinazi F.G.
        Endogenous opioids and social behavior.
        Neurosci Biobehav Rev. 1980; 4: 473-487
        • Moles A.
        • Kieffer B.L.
        • D’Amato F.R.
        Deficit in attachment behavior in mice lacking the mu-opioid receptor gene.
        Science. 2004; 304: 1983-1986
        • Hsu D.T.
        • Sanford B.J.
        • Meyers K.K.
        • Love T.M.
        • Hazlett K.E.
        • Wang H.
        • et al.
        Social feedback activates the endogenous opioid system.
        Mol Psychiatry 2013. 2013; 18: 1147
        • Roberts A.J.
        • McDonald J.S.
        • Heyser C.J.
        • Kieffer B.L.
        • Matthes H.W.
        • Koob G.F.
        • et al.
        mu-Opioid receptor knockout mice do not self-administer alcohol.
        J Pharmacol Exp Ther. 2000; 293: 1002-1008
        • Unterwald E.M.
        Regulation of opioid receptors by cocaine.
        Ann N Y Acad Sci. 2001; 937: 74-92
        • Smith K.S.
        • Berridge K.C.
        Opioid limbic circuit for reward: Interaction between hedonic hotspots of nucleus accumbens and ventral pallidum.
        J Neurosci. 2007; 27: 1594-1605

      Linked Article