Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients

Pharmacogenomics. 2011 Nov;12(11):1525-33. doi: 10.2217/pgs.11.96. Epub 2011 Sep 8.

Abstract

Aim: The present study explored the integrative effect of genes encoding methadone pharmacokinetic and pharmacodynamic pathways on methadone maintenance doses in Han Chinese Patients.

Materials & 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adult
  • Alleles
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • China
  • Cytochrome P-450 CYP2B6
  • Dose-Response Relationship, Drug*
  • Female
  • Genetic Association Studies
  • Haplotypes
  • Heroin Dependence / drug therapy*
  • Humans
  • Male
  • Methadone / pharmacokinetics
  • Methadone / therapeutic use*
  • Middle Aged
  • Opiate Substitution Treatment*
  • Oxidoreductases, N-Demethylating / genetics*
  • Polymorphism, Genetic
  • Protein-Serine-Threonine Kinases / genetics*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Opioid, mu / genetics*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • OPRM1 protein, human
  • Receptors, Dopamine D2
  • Receptors, Opioid, mu
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
  • ANKK1 protein, human
  • Protein-Serine-Threonine Kinases
  • Methadone