Dopaminergic pathway polymorphisms and heroin addiction: further support for association of CSNK1E variants

Pharmacogenomics. 2014 Dec;15(16):2001-9. doi: 10.2217/pgs.14.145.

Abstract

Background & aim: The dopaminergic pathways have been implicated in the etiology of drug addictions. The aim of this study was to determine if variants in dopaminergic genes are associated with heroin addiction.

Materials & methods: The study includes 828 former heroin addicts and 232 healthy controls, of predominantly European ancestry. Ninety seven SNPs (13 genes) were analyzed.

Results: Nine nominally significant associations were observed at CSNK1E, ANKK1, DRD2 and DRD3.

Conclusion: The results support our previous report of association of CSNK1E SNP rs1534891 with protection from heroin addiction. CSNK1E interacts with circadian rhythms and DARPP-32 and has been implicated in negative regulation of sensitivity to opioids in rodents. It may be a target for drug addiction treatment. Original submitted 8 August 2014; Revision submitted 8 October 2014.

Keywords: SNP rs1534891; casein kinase 1ε; circadian rhythms; dopaminergic reward pathways; heroin addiction.

Publication types

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

MeSH terms

  • Adult
  • Analgesics, Opioid / adverse effects
  • Casein Kinase 1 epsilon / genetics*
  • Circadian Rhythm / genetics
  • Dopamine / genetics
  • Dopamine / metabolism*
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / genetics
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Heroin Dependence / genetics*
  • Heroin Dependence / pathology
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • White People

Substances

  • Analgesics, Opioid
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • PPP1R1B protein, human
  • Casein Kinase 1 epsilon
  • Dopamine