Interindividual variability in the prevalence of OPRM1 and CYP2B6 gene variations may identify drug-susceptible populations

J Anal Toxicol. 2011 Sep;35(7):431-7. doi: 10.1093/anatox/35.7.431.

Abstract

Methadone is used worldwide for the treatment of heroin addiction; however, fatal poisonings are increasingly reported. The prevalence of CYP2B6 and μ-opioid receptor (OPRM1) gene variations were examined between a postmortem population where the deaths were associated with methadone and a live nondrug-using control population using Taqman™ SNP Genotyping assays. The CYP2B6*6 allele was higher in the postmortem population, but the difference was not significant (P = 0.92). The CYP2B6 T750C promoter variation was similar in frequency for both populations. Linkage between T750C and CYP2B6*6 was identified for both populations (P < 0.01). The prevalence of the OPRM1 A118G variation was significantly higher in the control population (P = 0.0046), which might indicate a protective mechanism against opioid toxicity. Individual susceptibility to methadone may be determined by screening for CYP2B6*6.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Case-Control Studies
  • Cytochrome P-450 CYP2B6
  • Female
  • Forensic Genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Methadone / pharmacokinetics
  • Methadone / poisoning*
  • Middle Aged
  • Oxidoreductases, N-Demethylating / genetics*
  • Poisoning / genetics
  • Poisoning / mortality
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Receptors, Opioid, mu / genetics*
  • Sex Factors
  • Young Adult

Substances

  • OPRM1 protein, human
  • Receptors, Opioid, mu
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
  • Methadone