Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment

Prog Neuropsychopharmacol Biol Psychiatry. 2008 Oct 1;32(7):1722-7. doi: 10.1016/j.pnpbp.2008.07.009. Epub 2008 Jul 17.

Abstract

Background: Genetic variations of the dopamine and opioid receptors could influence the response to methadone maintenance treatment (MMT).

Methods: We included 238 MMT patients according to their response to treatment and methadone dosing, along with 217 subjects without substance dependence. All were genotyped for polymorphisms of the dopamine D1, D2, micro-opioid and delta-opioid receptor genes.

Results: The polymorphisms of the micro-opioid (118A>G), delta-opioid (921T>C), dopamine D1 (DdeI) and D2 (TaqI A) receptor genes were not associated with response to MMT and methadone dosing, whereas an association was found with the dopamine D2 receptor (DRD2) 957C>T polymorphism. The 957CC carriers were more frequently non-responders to treatment (OR=2.4; p=0.02) and presented a fourfold shorter period of negative urine screening (p=0.02). No significant differences in allele frequencies were observed between the MMT patients and the control group, suggesting no association of the analyzed polymorphisms with opioid dependence.

Conclusions: These results suggest that DRD2 genotype may contribute to the understanding of the interindividual variability to the response to MMT.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Heroin Dependence / drug therapy*
  • Heroin Dependence / genetics*
  • Heroin Dependence / physiopathology
  • Humans
  • Male
  • Methadone / administration & dosage*
  • Middle Aged
  • Narcotics / administration & dosage*
  • Pharmacogenetics
  • Polymorphism, Genetic*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Opioid / genetics*

Substances

  • Narcotics
  • Receptors, Dopamine D2
  • Receptors, Opioid
  • Methadone