title: Variability of response to methadone: genome-wide DNA methylation analysis in two independent cohorts.
abstract: OBJECTIVE
  Methadone 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.
  
  
  METHODS
  Subjects 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Our results indicate that differentially methylated sites are associated with methadone daily dose and give insights into the molecular pathways underlying this interindividual dose variability.
authors.affiliation: Inserm, UMR-S 1144, Paris, F-75006, France.|Université Paris Descartes, UMR-S 1144, Paris, F-75006, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, F-75013, France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Marie-Claire
authors.affiliation: Unit of Pharmacogenetics & Clinical Psychopharmacology, Centre for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University, Hospital of Cery, Prilly-Lausanne, Switzerland.
authors.forename: Severine
authors.initials: S
authors.lastname: Crettol
authors.affiliation: Bioinformatics Platform Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cagnard
authors.affiliation: Inserm, UMR-S 1144, Paris, F-75006, France.|Université Paris Descartes, UMR-S 1144, Paris, F-75006, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, F-75013, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bloch
authors.affiliation: Inserm, UMR-S 1144, Paris, F-75006, France.|Université Paris Descartes, UMR-S 1144, Paris, F-75006, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, F-75013, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mouly
authors.affiliation: Inserm, UMR-S 1144, Paris, F-75006, France.|Université Paris Descartes, UMR-S 1144, Paris, F-75006, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, F-75013, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.affiliation: Inserm, UMR-S 1144, Paris, F-75006, France.|Université Paris Descartes, UMR-S 1144, Paris, F-75006, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, F-75013, France.|Psychiatry Department, Fernand Widal Hospital, Assistance Publique - Hôpitaux de Paris, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.affiliation: Inserm, UMR-S 1144, Paris, F-75006, France.|Université Paris Descartes, UMR-S 1144, Paris, F-75006, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, F-75013, France.|Psychiatry Department, Fernand Widal Hospital, Assistance Publique - Hôpitaux de Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lepine
authors.affiliation: Unit of Pharmacogenetics & Clinical Psychopharmacology, Centre for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University, Hospital of Cery, Prilly-Lausanne, Switzerland.
authors.forename: Chin
authors.initials: C
authors.lastname: Eap
authors.affiliation: Inserm, UMR-S 1144, Paris, F-75006, France.|Université Paris Descartes, UMR-S 1144, Paris, F-75006, France.|Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, F-75013, France.|Psychiatry Department, Fernand Widal Hospital, Assistance Publique - Hôpitaux de Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Vorspan
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D016000:Cluster Analysis; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone
keywords: DNA methylation; addiction; biomarkers; epigenetics; heroin; methadone