Centre for Forensic Sciences, Bournemouth University, Dorset, UK.
Clin Pharmacol Ther. 2010 Sep;88(3):383-9. doi: 10.1038/clpt.2010.127. Epub 2010 Jul 28.
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 CYP2B66 and A118G.
美沙酮是一种被广泛用于治疗海洛因成瘾的药物；然而，多年来已有许多与美沙酮使用相关的致命中毒事件报告。我们研究了 CYP2B6 和 μ-阿片受体（OPRM1）基因变异与美沙酮中毒易感性之间的关联。从 40 名因美沙酮中毒而死亡的个体的死后全血中提取基因组 DNA。通过 SNP 基因分型确定 CYP2B64、9 和6 等位基因和 OPRM1 A118G 变异体的存在。CYP2B64、9 和6 等位基因与血液中美沙酮浓度升高相关（P<0.05）。OPRM1 A118G 也与血液中美沙酮浓度升高相关，但未达到统计学显著性水平（P=0.39）。在这些与美沙酮相关的死亡中，OPRM1 118GA 与死后苯二氮䓬浓度升高相关（P=0.04），这一发现与吗啡相关的死亡无关。在治疗过程中，通过 CYP2B6*6 和 A118G 筛查，可以部分评估美沙酮相关致死的风险。
