ABCB1, SLC22A1, COMT, and OPRM1 genotypes: Study of their influence on plasma methadone levels and clinical response to methadone maintenance treatment in opioid use disorder

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BACKGROUND: Opioid use disorder (OUD) is an emerging and global public health concern, and its management remains inadequate, notably due to a lack of biomarkers, except for the CYP2B6 genetic polymorphisms. OBJECTIVES: Hence, the aim of this study was to assess the influence of genetic polymorphisms of ABCB1, SLC22A1, COMT, and OPRM1 on biological parameters and clinical response in patients receiving methadone maintenance treatment (MMT). METHODS: A subgroup of 72 patients treated by MMT was genotyped for ABCB1 (rs1045642; rs2032582), SLC22A1 (rs12208357; rs72552763; rs113569197), COMT (rs4680), and OPRM1 (rs1799971) from Opioid PhArmacoLogy (OPAL), a clinical survey of patients suffering from OUD. Associations of these polymorphisms and both clinical and pharmacological (plasma methadone levels) responses were investigated. RESULTS: All polymorphisms tested were not associated with (R,S)-methadone concentrations/doses (concentrations relative to doses), (R)-methadone concentrations/doses nor (S)-methadone concentrations/doses in bivariate analyses with codominant and recessive models. Also, polymorphisms tested were not related to clinical response (opiate cessation) during MMT in treated patients. The main limitations of our study were the sample size and the absence of polygenic analyses. CONCLUSION: This study found no evidence to support the use of genotyping for polymorphisms in the ABCB1, SLC22A1, COMT, and OPRM1 genes in a clinical setting for the management of MMT in OUD.

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