Orna Levran1, Einat Peles2, Matthew Randesi3, Joel Correa da Rosa4, Jurg Ott5, John Rotrosen6, Miriam Adelson7, Mary Jeanne Kreek3. 1. The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA. Electronic address: levrano@rockefeller.edu. 2. Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Tel Aviv Elias Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA. 4. Center for Clinical and Translational Science, The Rockefeller University, New York, NY, USA. 5. Institute of Psychology, Chinese Academy of Sciences, Beijing, China; The Laboratory of Statistical Genetics, The Rockefeller University, New York, NY, USA. 6. VA New York Harbor Healthcare System and NYU School of Medicine, New York, NY, USA. 7. The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA; Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Tel Aviv Elias Sourasky Medical Center, Tel Aviv, Israel; Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Las Vegas, NV, USA.
Abstract
BACKGROUND: Drug addiction, a leading health problem, is a chronic brain disease with a significant genetic component. Animal models and clinical studies established the involvement of glutamate and GABA neurotransmission in drug addiction. This study was designed to assess if 258 variants in 27 genes of these systems contribute to the vulnerability to develop drug addiction. METHODS: Four independent analyses were conducted in a sample of 1860 subjects divided according to drug of abuse (heroin or cocaine) and ancestry (African and European). RESULTS: A total of 11 SNPs in eight genes showed nominally significant associations (P<0.01) with heroin and/or cocaine addiction in one or both ancestral groups but the associations did not survive correction for multiple testing. Of these SNPs, the GAD1 upstream SNP rs1978340 is potentially functional as it was shown to affect GABA concentrations in the cingulate cortex. In addition, SNPs GABRB3 rs7165224; DBI rs12613135; GAD1 SNPs rs2058725, rs1978340, rs2241164; and GRIN2A rs1650420 were previously reported in associations with drug addiction or related phenotypes. CONCLUSIONS: The study supports the involvement of genetic variation in the glutamatergic and GABAergic systems in drug addiction with partial overlap in susceptibility loci between cocaine and heroin addiction.
BACKGROUND:Drug addiction, a leading health problem, is a chronic brain disease with a significant genetic component. Animal models and clinical studies established the involvement of glutamate and GABA neurotransmission in drug addiction. This study was designed to assess if 258 variants in 27 genes of these systems contribute to the vulnerability to develop drug addiction. METHODS: Four independent analyses were conducted in a sample of 1860 subjects divided according to drug of abuse (heroin or cocaine) and ancestry (African and European). RESULTS: A total of 11 SNPs in eight genes showed nominally significant associations (P<0.01) with heroin and/or cocaine addiction in one or both ancestral groups but the associations did not survive correction for multiple testing. Of these SNPs, the GAD1 upstream SNP rs1978340 is potentially functional as it was shown to affect GABA concentrations in the cingulate cortex. In addition, SNPs GABRB3rs7165224; DBIrs12613135; GAD1 SNPs rs2058725, rs1978340, rs2241164; and GRIN2Ars1650420 were previously reported in associations with drug addiction or related phenotypes. CONCLUSIONS: The study supports the involvement of genetic variation in the glutamatergic and GABAergic systems in drug addiction with partial overlap in susceptibility loci between cocaine and heroin addiction.
Authors: Stefano Marenco; Antonina A Savostyanova; Jan Willem van der Veen; Matthew Geramita; Alexa Stern; Alan S Barnett; Bhaskar Kolachana; Eugenia Radulescu; Fengyu Zhang; Joseph H Callicott; Richard E Straub; Jun Shen; Daniel R Weinberger Journal: Neuropsychopharmacology Date: 2010-03-31 Impact factor: 7.853
Authors: Chao Tian; Roman Kosoy; Rami Nassir; Annette Lee; Pablo Villoslada; Lars Klareskog; Lennart Hammarström; Henri-Jean Garchon; Ann E Pulver; Michael Ransom; Peter K Gregersen; Michael F Seldin Journal: Mol Med Date: 2009-08-27 Impact factor: 6.354
Authors: Giovanni Addolorato; Lorenzo Leggio; F Woodward Hopf; Marco Diana; Antonello Bonci Journal: Neuropsychopharmacology Date: 2011-10-26 Impact factor: 7.853
Authors: Gil Atzmon; Li Hao; Itsik Pe'er; Christopher Velez; Alexander Pearlman; Pier Francesco Palamara; Bernice Morrow; Eitan Friedman; Carole Oddoux; Edward Burns; Harry Ostrer Journal: Am J Hum Genet Date: 2010-06-11 Impact factor: 11.025
Authors: Puja K Parekh; Ryan W Logan; Kyle D Ketchesin; Darius Becker-Krail; Micah A Shelton; Mariah A Hildebrand; Kelly Barko; Yanhua H Huang; Colleen A McClung Journal: J Neurosci Date: 2019-04-08 Impact factor: 6.167