title: Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients.
abstract: OBJECTIVE
  The present study explored the integrative effect of genes encoding methadone pharmacokinetic and pharmacodynamic pathways on methadone maintenance doses in Han Chinese Patients.
  
  
  METHODS
  Genomic DNA was extracted from 321 opioid-dependent patients and 202 healthy controls, and realtime-PCR and PCR-RFLP were conducted to determine the genotypes.
  
  
  RESULTS
  Pair-wise comparisons revealed that carriers of the variants ABCB1 3435C>T or CYP2B6 516G>T alleles were more likely to require a higher methadone dose than noncarriers (both p < 0.0001). On the other hand, carriers of the variant DRD2 -214A>G or 939C>T allele had a twofold chance of requiring a lower methadone dose than noncarriers (p = 0.001). Proportional odds regression with adjustment of cofactors demonstrated that ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genetic variants were jointly correlated with optimal methadone dose (adjusted r(2) = 53%).
  
  
  CONCLUSIONS
  These findings provide new insight to the fact that the interindividual variability of methadone dosage requirement is polygenetic and cannot be explained by a single-gene effect.
authors: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors: Chin-Chuan
authors: CC
authors: Hung
authors: Mu-Han
authors: MH
authors: Chiou
authors: Bo-Hau
authors: BH
authors: Huang
authors: Yow-Wen
authors: YW
authors: Hsieh
authors: Tsung-Jen
authors: TJ
authors: Hsieh
authors: Chieh-Liang
authors: CL
authors: Huang
authors: Hsien-Yuan
authors: HY
authors: Lane
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002681:China; D065702:Cytochrome P-450 CYP2B6; D004305:Dose-Response Relationship, Drug; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006556:Heroin Dependence / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008691:Methadone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C485764:OPRM1 protein, human; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D008691:Methadone