Association of Alcohol or Other Drug Dependence with Alleles of the μ Opioid Receptor Gene (OPRM1)

Authors

  • Henry R. Kranzler,

    Corresponding author
    1. Alcohol Research Center, Department of Psychiatry (H.R.K, C.A.H.-A.), University of Connecticut Health Center, Farmington, Connecticut; Department of Psychiatry (J.G.), VA Connecticut Healthcare System, West Haven Campus, West Haven, Connecticut; and the Department of Psychiatry (J.G., S.O.), Yale University School of Medicine, West Haven, Connecticut; and the Department of Molecular and Medical Pharmacology (D.K.), University of California at Los Angeles, School of Medicine, Los Angeles, California.
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  • Joel Gelernter,

    1. Alcohol Research Center, Department of Psychiatry (H.R.K, C.A.H.-A.), University of Connecticut Health Center, Farmington, Connecticut; Department of Psychiatry (J.G.), VA Connecticut Healthcare System, West Haven Campus, West Haven, Connecticut; and the Department of Psychiatry (J.G., S.O.), Yale University School of Medicine, West Haven, Connecticut; and the Department of Molecular and Medical Pharmacology (D.K.), University of California at Los Angeles, School of Medicine, Los Angeles, California.
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  • Stephanie O'Malley,

    1. Alcohol Research Center, Department of Psychiatry (H.R.K, C.A.H.-A.), University of Connecticut Health Center, Farmington, Connecticut; Department of Psychiatry (J.G.), VA Connecticut Healthcare System, West Haven Campus, West Haven, Connecticut; and the Department of Psychiatry (J.G., S.O.), Yale University School of Medicine, West Haven, Connecticut; and the Department of Molecular and Medical Pharmacology (D.K.), University of California at Los Angeles, School of Medicine, Los Angeles, California.
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  • Carlos A. Hernandez-Avila,

    1. Alcohol Research Center, Department of Psychiatry (H.R.K, C.A.H.-A.), University of Connecticut Health Center, Farmington, Connecticut; Department of Psychiatry (J.G.), VA Connecticut Healthcare System, West Haven Campus, West Haven, Connecticut; and the Department of Psychiatry (J.G., S.O.), Yale University School of Medicine, West Haven, Connecticut; and the Department of Molecular and Medical Pharmacology (D.K.), University of California at Los Angeles, School of Medicine, Los Angeles, California.
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  • Daniel Kaufman

    1. Alcohol Research Center, Department of Psychiatry (H.R.K, C.A.H.-A.), University of Connecticut Health Center, Farmington, Connecticut; Department of Psychiatry (J.G.), VA Connecticut Healthcare System, West Haven Campus, West Haven, Connecticut; and the Department of Psychiatry (J.G., S.O.), Yale University School of Medicine, West Haven, Connecticut; and the Department of Molecular and Medical Pharmacology (D.K.), University of California at Los Angeles, School of Medicine, Los Angeles, California.
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  • This work was supported by the National Institutes of Health Grants K02-AA00239, P50-AA03510, R01-AA11330, K02-AA00171, R0l-DA05592, K02-MH01387, and M01-RR06192 (General Clinical Research Center), and the U.S. Department of Veterans Affairs (The VA-Yale Alcoholism Research Center).

Reprint requests: Henry R Kranzler, M.D., Department of Psychiatry, MC-2103, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030.

Abstract

Opioidergic neurotransmission and, specifically, the μ opioid receptor have been implicated in the reinforcing effects of a variety of drugs of abuse. Consequently, the present study examined the association of a polymorphic (CA)n repeat at the OPRM1 locus (the gene coding for the μ opioid receptor) to alcohol or drug dependence in 320 Caucasian and 108 African-American substance-dependent or control subjects. Among Caucasians, suggestion of a modest association, which could be interpreted as statistically significant (p= 0.03), was observed between OPRMl alleles and substance (alcohol, cocaine, or opioid) dependence. Analysis by specific substance showed only a trend level association to alcohol dependence. Comparisons among African Americans yielded no evidence for association. Further studies of the association between alleles of the OPRM1 gene and substance dependence appear warranted, particularly if they use a family-based approach to control for population stratication. Phenotypes other than a broad diagnostic categorization, such as opioid antagonist effects on drinking behavior in alcoholics, may provide more consistent evidence of a role for OPRMl in behavioral variability.

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