Variability of response to methadone: genome-wide DNA methylation analysis in two independent cohorts.

AIMMethadone maintenance treatment is characterized by large interindividual dose variability. The aim of this study was to evaluate whether DNA methylations are associated with daily dose of methadone.MATERIALS & METHODSSubjects stabilized at high (n = 12) or low (n = 12) methadone doses were selected from two independent cohorts (French and Swiss). DNA methylation patterns were analyzed using HumanMethylation450 BeadChips.RESULTSIn total, 584 differentially methylated sites were identified in the French cohort corresponding to 352 genes. Of these, 26 were replicated in the Swiss cohort. The methylation status of 13 genes varied similarly in both cohorts and calcium signaling pathway was significantly enriched.CONCLUSIONOur results indicate that differentially methylated sites are associated with methadone daily dose and give insights into the molecular pathways underlying this interindividual dose variability.KEYWORDSDNA methylation, addiction, biomarkers, epigenetics, heroin, methadone