Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients
| العنوان: | Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients |
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| المؤلفون: | Bo-Hau Huang, Hsien-Yuan Lane, Yow-Wen Hsieh, Mu-Han Chiou, Tsung-Jen Hsieh, Chieh-Liang Huang, Chin-Chuan Hung |
| المصدر: | Pharmacogenomics. 12:1525-1533 |
| بيانات النشر: | Future Medicine Ltd, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, Oncology, China, medicine.medical_specialty, Methadone maintenance, ATP Binding Cassette Transporter, Subfamily B, Receptors, Opioid, mu, Protein Serine-Threonine Kinases, Pharmacology, Internal medicine, Genotype, Opiate Substitution Treatment, Genetics, medicine, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Allele, Alleles, Genetic Association Studies, ANKK1, Polymorphism, Genetic, Dose-Response Relationship, Drug, Heroin Dependence, Receptors, Dopamine D2, business.industry, Haplotype, Oxidoreductases, N-Demethylating, Middle Aged, Cytochrome P-450 CYP2B6, Haplotypes, Pharmacodynamics, Molecular Medicine, Female, Aryl Hydrocarbon Hydroxylases, business, Methadone, medicine.drug |
| الوصف: | 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 |
| تدمد: | 1744-8042 1462-2416 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ba364e57490d420d752211bb9310361Test https://doi.org/10.2217/pgs.11.96Test |
| رقم الانضمام: | edsair.doi.dedup.....5ba364e57490d420d752211bb9310361 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17448042 14622416 |
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