Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.
Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.



Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT).



Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; pcorrected=0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; pcorrected=0.041) (HC vs. NOD).



This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction.
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: randesm@rockefeller.edu.
Matthew
M
Randesi
Central Committee on the Treatment of Heroin Addicts (CCBH), Utrecht, The Netherlands; Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
Wim
W
van den Brink
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Orna
O
Levran
Central Committee on the Treatment of Heroin Addicts (CCBH), Utrecht, The Netherlands; Parnassia Addiction Research Centre (PARC, Brijder Addiction Treatment), PO Box 53002, 2505 AA, The Hague, The Netherlands.
Peter
P
Blanken
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Eduardo R
ER
Butelman
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Vadim
V
Yuferov
Center for Clinical and Translational Science, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Joel Correa
JC
da Rosa
Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China; Laboratory of Statistical Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Jurg
J
Ott
Central Committee on the Treatment of Heroin Addicts (CCBH), Utrecht, The Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, The Netherlands.
Jan M
JM
van Ree
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Mary Jeanne
MJ
Kreek
D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use; D005260:Female; D003932:Heroin / Q000627:therapeutic use; D006556:Heroin Dependence / Q000235:genetics* / Q000534:rehabilitation; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000235:genetics* / Q000534:rehabilitation; D020641:Polymorphism, Single Nucleotide; D011498:Protein Precursors / Q000235:genetics*; D011957:Receptors, Opioid / Q000235:genetics*; D017465:Receptors, Opioid, delta / Q000235:genetics*
D000701:Analgesics, Opioid; D011498:Protein Precursors; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C121527:prepronociceptin; D003932:Heroin; D008691:Methadone
Heroin addiction; Heroin-assisted treatment; Non-dependent opioid use; Opioid genes; rs2236861
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