Matthew Randesi1, Wim van den Brink2, Orna Levran3, Peter Blanken4, Eduardo R Butelman3, Vadim Yuferov3, Joel Correa da Rosa5, Jurg Ott6, Jan M van Ree7, Mary Jeanne Kreek3. 1. Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: randesm@rockefeller.edu. 2. 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. 3. Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. 4. 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. 5. Center for Clinical and Translational Science, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. 6. 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. 7. Central Committee on the Treatment of Heroin Addicts (CCBH), Utrecht, The Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, The Netherlands.
Abstract
BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.
Authors: Elliot C Nelson; Michael T Lynskey; Andrew C Heath; Naomi Wray; Arpana Agrawal; Fiona L Shand; Anjali K Henders; Leanne Wallace; Alexandre A Todorov; Andrew J Schrage; Pamela A F Madden; Louisa Degenhardt; Nicholas G Martin; Grant W Montgomery Journal: Addict Biol Date: 2012-04-13 Impact factor: 4.280
Authors: Francesca Ducci; Alec Roy; Pei-Hong Shen; Qiaoping Yuan; Nicole P Yuan; Colin A Hodgkinson; Lynn R Goldman; David Goldman Journal: Am J Psychiatry Date: 2009-07-15 Impact factor: 18.112
Authors: O Levran; D Londono; K O'Hara; D A Nielsen; E Peles; J Rotrosen; P Casadonte; S Linzy; M Randesi; J Ott; M Adelson; M J Kreek Journal: Genes Brain Behav Date: 2008-06-02 Impact factor: 3.449
Authors: Xiaoling Xuei; Leah Flury-Wetherill; Laura Bierut; Danielle Dick; John Nurnberger; Tatiana Foroud; Howard J Edenberg Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2007-10-05 Impact factor: 3.568
Authors: Beate Beer; Robert Erb; Marion Pavlic; Hanno Ulmer; Salvatore Giacomuzzi; Yvonne Riemer; Herbert Oberacher Journal: PLoS One Date: 2013-09-25 Impact factor: 3.240
Authors: Vadim Yuferov; Matthew Randesi; Eduardo R Butelman; Wim van den Brink; Peter Blanken; Jan M van Ree; Jürg Ott; Mary Jeanne Kreek Journal: Neurosci Lett Date: 2019-03-29 Impact factor: 3.046
Authors: Matthew Randesi; Wim van den Brink; Orna Levran; Peter Blanken; Jan M van Ree; Jurg Ott; Mary Jeanne Kreek Journal: Pharmacogenomics Date: 2019-04-15 Impact factor: 2.533
Authors: Matthew Randesi; Wim van den Brink; Orna Levran; Vadim Yuferov; Peter Blanken; Jan M van Ree; Jurg Ott; Mary Jeanne Kreek Journal: Pharmacogenomics Date: 2017-12-06 Impact factor: 2.533
Authors: Matthew Randesi; Orna Levran; Wim van den Brink; Peter Blanken; Jan M van Ree; Jurg Ott; Mary J Kreek Journal: Pharmacogenomics Date: 2020-08-06 Impact factor: 2.533
Authors: Arpana Agrawal; Paul W Jeffries; A Benjamin Srivastava; Vivia V McCutcheon; Michael T Lynskey; Andrew C Heath; Elliot C Nelson Journal: J Neurosci Res Date: 2020-05-28 Impact factor: 4.164
Authors: Vadim Yuferov; Eduardo R Butelman; Matthew Randesi; Wim van den Brink; Peter Blanken; Jan M van Ree; Mary Jeanne Kreek Journal: Neuropsychiatr Dis Treat Date: 2021-02-25 Impact factor: 2.570