ArticlePLoS genetics2016
Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response.Journal of clinical laboratory analysis · 2022Pooled it
- A systematic review of GWAS identified SNPs associated with outcomes of medications for opioid use disorder.Addiction science & clinical practice · 2021Pooled it
- Genetic polymorphisms in the opioid receptor delta 1 (OPRD1) gene are associated with methadone dose in methadone maintenance treatment for heroin dependence.Journal of human genetics · 2020Trial
- Effect of rilpivirine on the pharmacokinetics of methadone in HIV-Infected Chinese patients.Expert review of clinical pharmacology · 2019Trial
- Population-specific optimization of polygenic risk scores for breast cancer in East Asians.Genetics in medicine open · 2026Article
- ABCB1, SLC22A1, COMT, and OPRM1 genotypes: Study of their influence on plasma methadone levels and clinical response to methadone maintenance treatment in opioid use disorder.Fundamental & clinical pharmacology · 2025Article
- Association ofBalkan journal of medical genetics : BJMG · 2025Article
- The Relevance of Pharmacokinetic Biomarkers in Response to Methadone Treatment: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- AI-enhanced integration of genetic and medical imaging data for risk assessment of Type 2 diabetes.Nature communications · 2024Article
- A genome-wide association, polygenic risk score and sex study on opioid use disorder treatment outcomes.Scientific reports · 2023Article
- Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder.Nature communications · 2023Article
- Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment.International journal of molecular sciences · 2022Article
- Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity.CPT: pharmacometrics & systems pharmacology · 2022Article
- Association of the D-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment.Journal of human genetics · 2022Article
- Genomic and Personalized Medicine Approaches for Substance Use Disorders (SUDs) Looking at Genome-Wide Association Studies.Biomedicines · 2021Review
- 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
- Novel associations betweenPharmacogenomics · 2021Observational
- Risk Assessment for Heroin Use and Craving Score Using Polygenic Risk Score.Journal of personalized medicine · 2021Article
- CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations-Implication for Drug Safety, Dosing, and Individualized Therapy.Frontiers in genetics · 2021Review
- Pharmacogenomics of methadone: a narrative review of the literature.Pharmacogenomics · 2020Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.
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Registered trials
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