Cynthia Marie-Claire1,2,3, Severine Crettol4, Nicolas Cagnard5, Vanessa Bloch1,2,3, Stéphane Mouly1,2,3, Jean-Louis Laplanche1,2,3, Frank Bellivier1,2,3,6, Jean-Pierre Lepine1,2,3,6, Chin Eap4, Florence Vorspan1,2,3,6. 1. Inserm, UMR-S 1144, Paris, F-75006, France. 2. Université Paris Descartes, UMR-S 1144, Paris, F-75006, France. 3. Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, F-75013, France. 4. Unit of Pharmacogenetics & Clinical Psychopharmacology, Centre for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University, Hospital of Cery, Prilly-Lausanne, Switzerland. 5. Bioinformatics Platform Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 6. Psychiatry Department, Fernand Widal Hospital, Assistance Publique - Hôpitaux de Paris, France.
Abstract
AIM: 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. MATERIALS & 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. CONCLUSION: 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.
AIM: 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. MATERIALS & 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. CONCLUSION: 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.
Entities:
Keywords:
DNA methylation; addiction; biomarkers; epigenetics; heroin; methadone
Authors: Jose Vladimir Sandoval-Sierra; Francisco I Salgado García; Jeffrey H Brooks; Karen J Derefinko; Khyobeni Mozhui Journal: Clin Epigenetics Date: 2020-06-03 Impact factor: 6.551