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

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

Author information

1
Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.

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.

PMID:
21902500
DOI:
10.2217/pgs.11.96
[Indexed for MEDLINE]

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