OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths

This source preferred by Wei-Jun Liang

Authors: Bunten, H., Liang, W.-J., Pounder, D. and Osselton, D.M.

Journal: Clinical Pharmacology and Therapeutics

Volume: 88

Pages: 383-389

ISSN: 0009-9236

This data was imported from PubMed:

Authors: Bunten, H., Liang, W.J., Pounder, D.J., Seneviratne, C. and Osselton, D.

Journal: Clin Pharmacol Ther

Volume: 88

Issue: 3

Pages: 383-389

eISSN: 1532-6535

DOI: 10.1038/clpt.2010.127

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 micro-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 < or = 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.

This data was imported from Scopus:

Authors: Bunten, H., Liang, W.J., Pounder, D.J., Seneviratne, C. and Osselton, D.

Journal: Clinical Pharmacology and Therapeutics

Volume: 88

Issue: 3

Pages: 383-389

eISSN: 1532-6535

ISSN: 0009-9236

DOI: 10.1038/clpt.2010.127

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 ν-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 CYP2B66 and A118G. © 2010 American Society for Clinical Pharmacology and Therapeutics.

This data was imported from Web of Science (Lite):

Authors: Bunten, H., Liang, W.J., Pounder, D.J., Seneviratne, C. and Osselton, D.

Journal: CLINICAL PHARMACOLOGY & THERAPEUTICS

Volume: 88

Issue: 3

Pages: 383-389

ISSN: 0009-9236

DOI: 10.1038/clpt.2010.127

This data was imported from Europe PubMed Central:

Authors: Bunten, H., Liang, W.J., Pounder, D.J., Seneviratne, C. and Osselton, D.

Journal: Clinical pharmacology and therapeutics

Volume: 88

Issue: 3

Pages: 383-389

eISSN: 1532-6535

ISSN: 0009-9236

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 micro-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 < or = 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.

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