Synaptic Plasticity and Signal Transduction Gene Polymorphisms and Vulnerability to Drug Addictions in Populations of European or African Ancestry.

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.

• Authors: Orna Levran, Einat Peles, Matthew Randesi, Joel Correa da Rosa, Jurg Ott, John Rotrosen, Miriam Adelson, Mary Jeanne Kreek
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 21 Issue 11 Pg. 898-904 (Nov 2015) ISSN: 1755-5949 [Electronic] England
• PMID: 26384852 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• NF-kappa B p50 Subunit
• NFKB1 protein, human

Topics

• Black People
• Cocaine-Related Disorders (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Heroin Dependence (genetics)
• Humans
• Male
• NF-kappa B p50 Subunit (genetics)
• Neuronal Plasticity (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Signal Transduction (genetics)
• White People