title: Synaptic Plasticity and Signal Transduction Gene Polymorphisms and Vulnerability to Drug Addictions in Populations of European or African Ancestry.
abstract: OBJECTIVE
  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.
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
authors.forename: Orna
authors.initials: O
authors.lastname: Levran
authors.affiliation: 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.
authors.forename: Einat
authors.initials: E
authors.lastname: Peles
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Randesi
authors.affiliation: Center for Clinical and Translational Science, The Rockefeller University, New York, NY, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Correa da Rosa
authors.affiliation: Institute of Psychology, Chinese Academy of Sciences, Beijing, China.|The Laboratory of Statistical Genetics, The Rockefeller University, New York, NY, USA.
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.affiliation: VA New York Harbor Healthcare System, NYU School of Medicine, New York, NY, USA.
authors.forename: John
authors.initials: J
authors.lastname: Rotrosen
authors.affiliation: 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.
authors.forename: Miriam
authors.initials: M
authors.lastname: Adelson
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D044383:Black People; D019970:Cocaine-Related Disorders / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006556:Heroin Dependence / Q000235:genetics*; D006801:Humans; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D044465:White People; D001741:Black or African American
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human
keywords: African Americans; Cocaine addiction; Heroin addiction; Signal transduction; Synaptic plasticity