Opioids such as methadone and morphine are full agonists at the μ-opioid receptor, which is encoded by the gene OPRM1 on chromosome 6.6 OPRM1 has been the subject of intense interest, particularly the common missense single nucleotide polymorphism (SNP) rs1799971, but also non-coding variation, with dozens of candidate gene association studies having examined a wide range of phenotypes.12–14 Many of the initial claims about associations between the candidate missense variant rs1799971 and clinical phenotypes have not proven to be robust,15, 16 although modest effects do appear to be present.17, 18 In addition to OPRM1, studies have also examined the relationship between methadone metabolism and candidate polymorphisms in genes encoding cytochrome P450 enzymes, including CYP3A4, CYP2B6 and CYP2D6.19–21 Neither metabolic enzyme polymorphisms nor serum methadone levels (SMLs) have yet been shown to be reliable predictors of maintenance dose.22, 23 Genes related to both pharmacodynamics and pharmacokinetics may, however, influence each individual’s dosing needs.
