Orna Levran1, Einat Peles2,3, Matthew Randesi1, Joel Correa da Rosa4, Jurg Ott5,6, John Rotrosen7, Miriam Adelson1,2,8, Mary Jeanne Kreek1. 1. The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA. 2. Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Tel Aviv Elias Sourasky Medical Center, Tel Aviv, Israel. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. Center for Clinical and Translational Science, The Rockefeller University, New York, NY, USA. 5. Institute of Psychology, Chinese Academy of Sciences, Beijing, China. 6. The Laboratory of Statistical Genetics, The Rockefeller University, New York, NY, USA. 7. VA New York Harbor Healthcare System, NYU School of Medicine, New York, NY, USA. 8. Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Las Vegas, NV, USA.
Abstract
AIM: Drug addiction is characterized, in part, by deregulation of synaptic plasticity in circuits involved in reward, stress, cue learning, and memory. This study was designed to assess whether 185 variants in 32 genes central to synaptic plasticity and signal transduction contribute to vulnerability to develop heroin and/or cocaine addiction. METHODS: Analyses were conducted in a sample of 1860 subjects divided according to ancestry (African and European) and drug of abuse (heroin or cocaine). RESULTS: Eighteen SNPs in 11 genes (CDK5R1, EPHA4, EPHA6, FOSL2, MAPK3, MBP, MPDZ, NFKB1, NTRK2, NTSR1, and PRKCE) showed significant associations (P < 0.01), but the signals did not survive correction for multiple testing. SNP rs230530 in the NFKB1 gene, encoding the transcription regulator NF-kappa-B, was the only SNP indicated in both ancestry groups and both addictions. This SNP was previously identified in association with alcohol addiction. SNP rs3915568 in NTSR1, which encodes neurotensin receptor, and SNP rs1389752 in MPDZ, which encodes the multiple PDZ domain protein, were previously associated with heroin addiction or alcohol addiction, respectively. CONCLUSIONS: The study supports the involvement of genetic variation in signal transduction pathways in heroin and cocaine addiction and provides preliminary evidence suggesting several new risk or protective loci that may be relevant for diagnosis and treatment success.
AIM: Drug addiction is characterized, in part, by deregulation of synaptic plasticity in circuits involved in reward, stress, cue learning, and memory. This study was designed to assess whether 185 variants in 32 genes central to synaptic plasticity and signal transduction contribute to vulnerability to develop heroin and/or cocaine addiction. METHODS: Analyses were conducted in a sample of 1860 subjects divided according to ancestry (African and European) and drug of abuse (heroin or cocaine). RESULTS: Eighteen SNPs in 11 genes (CDK5R1, EPHA4, EPHA6, FOSL2, MAPK3, MBP, MPDZ, NFKB1, NTRK2, NTSR1, and PRKCE) showed significant associations (P < 0.01), but the signals did not survive correction for multiple testing. SNP rs230530 in the NFKB1 gene, encoding the transcription regulator NF-kappa-B, was the only SNP indicated in both ancestry groups and both addictions. This SNP was previously identified in association with alcohol addiction. SNP rs3915568 in NTSR1, which encodes neurotensin receptor, and SNP rs1389752 in MPDZ, which encodes the multiple PDZ domain protein, were previously associated with heroin addiction or alcohol addiction, respectively. CONCLUSIONS: The study supports the involvement of genetic variation in signal transduction pathways in heroin and cocaine addiction and provides preliminary evidence suggesting several new risk or protective loci that may be relevant for diagnosis and treatment success.
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