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.
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.
Authors: R Douglas Bruce; David E Moody; Frederick L Altice; Marc N Gourevitch; Gerald H Friedland Journal: Expert Rev Clin Pharmacol Date: 2013-05 Impact factor: 5.045
Authors: Richard C Crist; Toni-Kim Clarke; Alfonso Ang; Lisa M Ambrose-Lanci; Falk W Lohoff; Andrew J Saxon; Walter Ling; Maureen P Hillhouse; R Douglas Bruce; George Woody; Wade H Berrettini Journal: Neuropsychopharmacology Date: 2013-04-23 Impact factor: 7.853