title: Interindividual variability in the prevalence of OPRM1 and CYP2B6 gene variations may identify drug-susceptible populations.
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.
authors.affiliation: Centre for Forensic Sciences, Bournemouth University, Dorset, United Kingdom. hbunten@bournemouth.ac.uk
authors.forename: H
authors.initials: H
authors.lastname: Bunten
authors.forename: W J
authors.initials: WJ
authors.lastname: Liang
authors.forename: D J
authors.initials: DJ
authors.lastname: Pounder
authors.forename: C
authors.initials: C
authors.lastname: Seneviratne
authors.forename: D
authors.initials: D
authors.lastname: Osselton
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D053803:Forensic Genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008691:Methadone / Q000493:pharmacokinetics / Q000506:poisoning*; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D011041:Poisoning / Q000235:genetics / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012737:Sex Factors; D055815:Young Adult
chemical_list: C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; D008691:Methadone