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

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.