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OPRM1 and CYP2B6 Gene Variants as Risk Factors in Methadone‐Related Deaths
Author(s) -
Bunten H,
Liang W J,
Pounder D J,
Seneviratne C,
Osselton D
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2010.127
Subject(s) - methadone , medicine , cyp2b6 , genotyping , opioid , genotype , pharmacology , anesthesia , gene , biology , genetics , cyp3a4 , receptor , cytochrome p450 , metabolism
Methadone is a medication valued for its effectiveness in the treatment of heroin addiction; however, many fatal poisonings associated with its use have been reported over the years. We have examined the association between CYP2B6 and µ‐opioid receptor ( OPRM1 ) gene variations and apparent susceptibility to methadone poisoning. Genomic DNA was extracted from postmortem whole blood of 40 individuals whose deaths were attributed to methadone poisoning. The presence of CYP2B6*4,*9, and *6 alleles and the OPRM1 A118G variant was determined by SNP genotyping. CYP2B6 *4, *9, and *6 alleles were found to be associated with higher postmortem methadone concentrations in blood ( P ≤ 0.05). OPRM1 A118G was also associated with higher postmortem methadone concentrations in blood but not to a level of statistical significance ( P = 0.39). In these methadone‐related deaths, OPRM1 118GA was associated with higher postmortem benzodiazepine concentrations ( P = 0.04), a finding not associated with morphine‐related deaths. The risk of a methadone‐related fatality during treatment may be evaluated in part by screening for CYP2B6*6 and A118G. Clinical Pharmacology & Therapeutics (2010) 88 3, 383–389. doi: 10.1038/clpt.2010.127