Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients
CC Hung, MH Chiou, BH Huang, YW Hsieh… - …, 2011 - Future Medicine
Pharmacogenomics, 2011•Future Medicine
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 …
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 …
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 r2 = 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.
Original submitted 4 May 2011; Revision submitted 8 July 2011
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