Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry

Orna Levran; Einat Peles; Matthew Randesi; Joel Correa da Rosa; Jurg Ott; John Rotrosen; Miriam Adelson; Mary Jeanne Kreek

doi:10.1016/j.pnpbp.2015.08.003

Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry

Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4:64:118-23. doi: 10.1016/j.pnpbp.2015.08.003. Epub 2015 Aug 12.

Authors

Orna Levran¹, Einat Peles², Matthew Randesi³, Joel Correa da Rosa⁴, Jurg Ott⁵, John Rotrosen⁶, Miriam Adelson⁷, Mary Jeanne Kreek³

Affiliations

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.

Keywords: Addiction; African Americans; Cocaine; GAD1, glutamate, GABA; Heroin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Black People / genetics
Black or African American / genetics
Case-Control Studies
Cocaine-Related Disorders / ethnology
Cocaine-Related Disorders / genetics*
Female
Genetic Association Studies
Genetic Predisposition to Disease*
Heroin Dependence / ethnology
Heroin Dependence / genetics*
Humans
Linkage Disequilibrium
Male
Polymorphism, Single Nucleotide*
Receptors, GABA-A / genetics*
Receptors, Glutamate / genetics*
White People / genetics

Substances

Receptors, GABA-A
Receptors, Glutamate

Abstract

Publication types

MeSH terms

Substances

Grants and funding