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CYP2B6 and OPRM1 gene variations predict methadone-related deaths
Hannah Bunten1, Wei-Jun Liang, Derrick Pounder
1Centre for Forensic Sciences, Bournemouth University, UK. hbunten@bournemouth.ac.uk
Addiction Biology
|December 16, 2010
Summary
Methadone fatalities are linked to specific gene variations. The CYP2B6*6 allele, indicating slow metabolism, correlated with high methadone levels, while the OPRM1 A118G allele GA correlated with benzodiazepine levels in fatal cases.
Area of Science:
- Pharmacogenetics
- Toxicology
- Clinical Pharmacology
Background:
- Methadone is frequently prescribed for pain and opioid use disorder.
- A significant number of methadone-associated deaths occur during the initial drug induction phase.
- Genetic factors may influence individual responses and risks associated with methadone treatment.
Purpose of the Study:
- To investigate the association between specific gene variations and methadone-related fatalities.
- To identify genetic markers that may predict increased risk during methadone therapy.
- To explore the role of genetic polymorphisms in methadone and co-administered drug concentrations in fatal cases.
Main Methods:
- Analysis of methadone-related fatalities.
- Genotyping for variations in genes involved in methadone metabolism and action, including CYP2B6 and OPRM1.
- Correlation of genetic data with post-mortem drug concentrations (methadone and benzodiazepines).
Main Results:
- A significant association was found between high methadone concentrations and the CYP2B6*6 allele, a marker for slow metabolizers.
- A significant correlation was observed between post-mortem benzodiazepine concentrations and the OPRM1 A118G allele GA in fatalities.
- These genetic variations may predispose individuals to adverse outcomes during methadone treatment.
Conclusions:
- The CYP2B6*6 allele may contribute to the risk of methadone fatality by influencing methadone concentrations.
- The OPRM1 A118G allele GA is associated with benzodiazepine levels in methadone-related deaths.
- Pre-prescription screening for these genetic variations could help mitigate serious adverse effects and reduce fatality risk.
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