ArticlePharmacogenomics and personalized medicine2012
ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics.
Article in Pharmacogenomics and personalized medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response.Journal of clinical laboratory analysis · 2022Pooled it
- Pooled it
- Association of the D-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment.Journal of human genetics · 2022Article
- Pharmacokinetic modeling of R and S-Methadone and their metabolites to study the effects of various covariates in post-operative children.CPT: pharmacometrics & systems pharmacology · 2021Article
- Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths.International journal of legal medicine · 2021Article
- Pharmacogenomics of methadone: a narrative review of the literature.Pharmacogenomics · 2020Review
- The impact of liver transplant recipient and donor genetic variability on tacrolimus exposure and transplant outcome.British journal of clinical pharmacology · 2019Article
- Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African-Americans with opioid use disorder.The pharmacogenomics journal · 2019Article
- GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence.The international journal of neuropsychopharmacology · 2018Article
- Pharmacogenetics of Opioid Use Disorder Treatment.CNS drugs · 2018Review
- Global genetic variation of select opiate metabolism genes in self-reported healthy individuals.The pharmacogenomics journal · 2018Article
- Pharmacogenetics of Methadone Response.Molecular diagnosis & therapy · 2018Review
- Methadone Dosage and Plasma Levels, SNPs of OPRM1 Gene and Age of First Drug Use Were Associated With Outcomes of Methadone Maintenance Treatment.Frontiers in genetics · 2018Article
- Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions.Pharmaceutical research · 2015Review
- A review of pharmacogenetic studies of substance-related disorders.Drug and alcohol dependence · 2015Review
- Opioid-induced respiratory depression: ABCB1 transporter pharmacogenetics.The pharmacogenomics journal · 2015Observational
- Pharmacogenetics of OPRM1.Pharmacology, biochemistry, and behavior · 2014Review
- Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction.Pharmacogenomics · 2013Article
- Pharmacogenetics of chronic pain and its treatment.Mediators of inflammation · 2013Review
- Association ofBasic and clinical neuroscienceArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic variability in ABCB1, encoding the P-glycoprotein efflux transporter, has been linked to altered methadone maintenance treatment dose requirements. However, subsequent studies have indicated that additional environmental or genetic factors may confound ABCB1 pharmacogenetics in different methadone maintenance treatment settings. There is evidence that genetic variability in OPRM1, encoding the mu opioid receptor, and ABCB1 may interact to affect morphine response in opposite ways. This study aimed to examine whether a similar gene-gene interaction occurs for methadone in methadone maintenance treatment.
methodsOpioid-dependent subjects (n = 119) maintained on methadone (15-300 mg/day) were genotyped for five single nucleotide polymorphisms of ABCB1 (61A > G; 1199G > A; 1236C > T; 2677G > T; 3435C > T), as well as for the OPRM1 118A > G single nucleotide polymorphism. Subjects' methadone doses and trough plasma (R)-methadone concentrations (C(trough)) were compared between ABCB1 haplotypes (with and without controlling for OPRM1 genotype), and between OPRM1 genotypes (with and without controlling for ABCB1 haplotype).
resultsAmong wild-type OPRM1 subjects, an ABCB1 variant haplotype group (subjects with a wild-type and 61A:1199G:1236C:2677T:3435T haplotype combination, or homozygous for the 61A:1199G:1236C:2677T:3435T haplotype) had significantly lower doses (median ± standard deviation 35 ± 5 versus 180 ± 65 mg/day, P < 0.01) and C(trough) (78 ± 22 versus 177 ± 97 ng/mL, P < 0.05) than ABCB1 wild-type subjects. Among subjects with the most common ABCB1 haplotype combination (wild-type with 61A:1199G:1236T:2677T:3435T), the OPRM1 118 A/G genotype was associated with a significantly higher C(trough) than 118 A/A (250 ± 126 versus 108 ± 36 ng/mL, P = 0.016). No ABCB1 haplotype group or OPRM1 genotype was associated with dose or C(trough) without taking into account confounding genetic variability at the other locus. Therefore, two interacting pharmacogenetic determinants of methadone maintenance treatment response were identified, ie, ABCB1, where variants are associated with lower methadone requirements, and OPRM1, where the variant is associated with higher methadone requirements.
conclusionThese opposing pharmacogenetic effects therefore need to be considered in combination when assessing methadone maintenance treatment pharmacogenetics.
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