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.
journal_name
Pharmacogenomicsjournal_title
Pharmacogenomicsauthors
Hung CC,Chiou MH,Huang BH,Hsieh YW,Hsieh TJ,Huang CL,Lane HYdoi
10.2217/pgs.11.96subject
Has Abstractpub_date
2011-11-01 00:00:00pages
1525-33issue
11eissn
1462-2416issn
1744-8042journal_volume
12pub_type
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