title: CYP2B6 and OPRM1 gene variations predict methadone-related deaths.
abstract: The largest proportion of methadone-associated deaths occurs during the drug induction phase. We analysed methadone-related fatalities for gene variations linked with methadone action. A significant association between high methadone concentrations and the CYP2B6*6 allele characteristic of the slow metabolizer phenotype was identified. We suggest that the risk of methadone fatality may be predetermined in part by the CYP2B6*6 allele. A significant correlation was also observed between post-mortem benzodiazepine concentrations and the OPRM1 A118G allele GA in methadone-related fatalities. Screening for these susceptibility variations prior to methadone prescription could assist in reducing the potential for serious adverse effects.
authors.affiliation: Centre for Forensic Sciences, Bournemouth University, UK. hbunten@bournemouth.ac.uk
authors.forename: Hannah
authors.initials: H
authors.lastname: Bunten
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Liang
authors.forename: Derrick
authors.initials: D
authors.lastname: Pounder
authors.forename: Collin
authors.initials: C
authors.lastname: Seneviratne
authors.forename: Michael David
authors.initials: MD
authors.lastname: Osselton
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001569:Benzodiazepines / Q000493:pharmacokinetics / Q000633:toxicity; D002423:Cause of Death; D065702:Cytochrome P-450 CYP2B6; D004357:Drug Synergism; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006556:Heroin Dependence / Q000097:blood / Q000401:mortality* / Q000534:rehabilitation*; D006801:Humans; D008691:Methadone / Q000493:pharmacokinetics / Q000633:toxicity*; D009020:Morphine / Q000493:pharmacokinetics; D009294:Narcotics / Q000493:pharmacokinetics / Q000633:toxicity*; D058850:Opiate Substitution Treatment / Q000009:adverse effects* / Q000401:mortality*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012307:Risk Factors
chemical_list: D009294:Narcotics; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D001569:Benzodiazepines; D009020:Morphine; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; D008691:Methadone