title: Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction.
abstract: OBJECTIVE
  The interindividual variability in the dose required for effective methadone maintenance treatment (MMT) for opioid addiction may be influenced in part by genetic variations in genes encoding pharmacodynamic factors of methadone. This study was conducted to identify some of these variants.
  
  
  METHODS
  This study focused on 11 genes encoding components of the opioidergic (OPRM1, POMC and ARRB2), the dopaminergic (ANKK1 and DRD2) and the glutamatergic pathways (GRIN1 and GRIN2A), as well as the neurotrophin system (NGFB, BDNF, NTRK1 and NTRK2). The study includes 227 Israeli patients undergoing stable MMT.
  
  
  RESULTS
  Out of the 110 variants analyzed, 12 SNPs (in BDNF, NTRK2, OPRM1, DRD2 and ANKK1) were associated with methadone dose (nominal p < 0.05). Of these SNPs, ANKK1 rs7118900 and DRD2 rs2283265 are known to affect gene expression. Logistic regression of five representative SNPs discriminated between individuals requiring a methadone dose of >120 mg/day and <120 mg/day (p = 0.019), and showed moderate sensitivity and specificity (AUC of 0.63 in receiver operating characteristic analysis).
  
  
  CONCLUSIONS
  This data should stimulate further research on the potential influence and clinical significance of these variants on MMT.
authors: Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA. levrano@rockefeller.edu
authors: Orna
authors: O
authors: Levran
authors: Einat
authors: E
authors: Peles
authors: Matthew
authors: M
authors: Randesi
authors: Xu
authors: X
authors: Shu
authors: Jurg
authors: J
authors: Ott
authors: Pei-Hong
authors: PH
authors: Shen
authors: Miriam
authors: M
authors: Adelson
authors: Mary Jeanne
authors: MJ
authors: Kreek
mesh_terms: D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D058850:Opiate Substitution Treatment / Q000379:methods; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D008691:Methadone
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