Open AccessSynaptic Plasticity and Signal Transduction Gene Polymorphisms and Vulnerability to Drug Addictions in Populations of European or African Ancestry
Author(s) -
Levran Orna,
Peles Einat,
Randesi Matthew,
Correa da Rosa Joel,
Ott Jurg,
Rotrosen John,
Adelson Miriam,
Kreek Mary Jeanne
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12450
Subject(s) - snp , single nucleotide polymorphism , addiction , biology , genetics , signal transduction , gene , neuroscience , genotype
Summary 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 SNP s in 11 genes ( CDK 5R1 , EPHA 4 , EPHA 6 , FOSL 2 , MAPK 3 , MBP , MPDZ , NFKB 1 , NTRK 2 , NTSR 1 , and PRKCE ) showed significant associations ( P < 0.01), but the signals did not survive correction for multiple testing. SNP rs230530 in the NFKB 1 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 NTSR 1 , 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.