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

被引：17

作者：

Marie-Claire, Cynthia ^{[1
,2
,3
]}

Crettol, Severine ^{[5
]}

Cagnard, Nicolas ^{[6
]}

Bloch, Vanessa ^{[1
,2
,3
]}

Mouly, Stephane ^{[1
,2
,3
]}

Laplanche, Jean-Louis ^{[1
,2
,3
]}

Bellivier, Frank ^{[1
,2
,3
,4
]}

Lepine, Jean-Pierre ^{[1
,2
,3
,4
]}

Eap, Chin ^{[5
]}

Vorspan, Florence ^{[1
,2
,3
,4
]}

机构：

[1] INSERM, UMR S 1144, F-75006 Paris, France

[2] Univ Paris 05, UMR S 1144, F-75006 Paris, France

[3] Univ Paris Diderot, Sorbonne Paris Cite, UMR S 1144, F-75013 Paris, France

[4] Fernand Widal Hosp, AP HP, Dept Psychiat, St Denis, France

[5] Univ Lausanne, Hosp Cery, Dept Psychiat, Unit Pharmacogenet & Clin Psychopharmacol,Ctr Psy, Prilly, Switzerland

[6] Univ Paris 05, Bioinformat Platform, Sorbonne Paris Cite, Paris, France

来源：

EPIGENOMICS | 2016年 / 8卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

addiction; biomarkers; DNA methylation; epigenetics; heroin; methadone; DEFICIT HYPERACTIVITY DISORDER; OPIOID DEPENDENCE; PLASMA-LEVELS; PSYCHIATRIC COMORBIDITY; CHILDHOOD MALTREATMENT; GENETIC POLYMORPHISMS; MAINTENANCE TREATMENT; DOSE METHADONE; ABCB1; ASSOCIATION;

D O I：

10.2217/epi.15.110

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：181 / 195

页数：15

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