Association of CYP2B6 and OPRM1 Genotypes with Methadone Dose Requirements and Serum Concentrations in a Vietnamese Cohorts.
| Title: | Association of CYP2B6 and OPRM1 Genotypes with Methadone Dose Requirements and Serum Concentrations in a Vietnamese Cohorts. |
|---|---|
| Authors: | Nguyen QG; Faculty Medical Technology, Hanoi Medical University, Hanoi, Vietnam.; Tran KC; Biochemistry Department, Hanoi Medical University, Hanoi, Vietnam.; Trinh TPD; Faculty Medical Technology, Hanoi Medical University, Hanoi, Vietnam.; Pham HT; Center for Family Medicine and Community Health Care, Hanoi Medical University Hospital, Hanoi, Vietnam.; Dang TND; Biochemistry Department, Hanoi Medical University, Hanoi, Vietnam. |
| Source: | Balkan journal of medical genetics : BJMG [Balkan J Med Genet] 2025 Oct 08; Vol. 28 (1), pp. 20250010. Date of Electronic Publication: 2025 Oct 08 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Sciendo Country of Publication: Poland NLM ID: 9806959 Publication Model: eCollection Cited Medium: Print ISSN: 1311-0160 (Print) Linking ISSN: 13110160 NLM ISO Abbreviation: Balkan J Med Genet Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Publication: [Warsaw, Poland] : Sciendo; Original Publication: Sofia, Bulgaria : DL&M Ltd., [1998-2001] |
| Abstract: | To characterize the prevalence of CYP2B6 and OPRM1 gene polymorphisms and evaluate their associations with serum methadone concentrations and dose requirements in Vietnamese patients undergoing methadone maintenance treatment (MMT). This cross-sectional study enrolled 200 patients with opioid dependence from multiple MMT clinics in Ninh Binh, Vietnam, between October 2023 and March 2024. Demographic, clinical, and behavioral data were collected using structured questionnaires. Blood samples were obtained for genotyping CYP2B6 (rs2279343 [785A>G], rs3745274 [516G>T], rs8192709 [64C>T]) and OPRM1 (A118G, rs1799971) using Sanger sequencing. Trough serum methadone concentrations were measured by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multivariable linear regression was performed to identify clinical and genetic factors associated with serum methadone concentrations, the concentration-to-dose ratio (CDR), and maintenance methadone dose. Among 200 participants (99% male, 96.9% Kinh ethnicity), the most common CYP2B6 diplotypes were *1/*4 (33.3%) and *4/*6 (23.7%), with the OPRM1 AG genotype present in 47.5%. Most patients (53.5%) had been on methadone treatment for over 3 years. In multivariable regression, the *1/*6 genotype was independently associated with lower maintenance dose (β = -26.33, 95% CI: -51.97, -0.69). The *2/*6 genotype was significantly associated with lower log serum methadone concentration (β = -2.485, 95% CI: -3.024, -1.947) and lower log CDR (β = -2.595, 95% CI: -3.145, -2.046). Most demographic, behavioral, and OPRM1 genotypes showed no significant associations. Specific CYP2B6 genotypes and SNPs significantly influence methadone pharmacokinetics in Vietnamese patients receiving MMT, although actual daily dose remains the most important determinant of serum levels. These findings highlight the potential role of genotype-guided methadone dosing in optimizing therapy for opioid dependence in Vietnamese populations.; (© 2025 Nguyen Quynh Giao et al.) |
| References: | J Pain Symptom Manage. 2024 Jan;67(1):39-49.e5. (PMID: 37757956); Br J Clin Pharmacol. 2024 Nov;90(11):2823-2836. (PMID: 38993001); PLoS One. 2020 Apr 17;15(4):e0231467. (PMID: 32302325); Pharmacogenet Genomics. 2022 Jan 1;32(1):31-38. (PMID: 34380995); Clin Pharmacokinet. 2016 Dec;55(12):1521-1533. (PMID: 27286724); J Anal Toxicol. 2011 Sep;35(7):431-7. (PMID: 21871151); Drug Metab Dispos. 2015 Jul;43(7):994-1001. (PMID: 25897175); Anesthesiology. 2015 Nov;123(5):1142-53. (PMID: 26389554); Clin Pharmacol Ther. 2024 Mar;115(3):506-514. (PMID: 38009933); Addict Biol. 2024 Jan;29(1):e13355. (PMID: 38221808); Mol Psychiatry. 2017 Mar;22(3):346-352. (PMID: 28115739); Pharmacogenet Genomics. 2013 Feb;23(2):84-93. (PMID: 23249875); J Clin Lab Anal. 2022 Nov;36(11):e24750. (PMID: 36305091); Iran Biomed J. 2021 Feb 06;25(3):220-5. (PMID: 33546554); Bosn J Basic Med Sci. 2021 Apr 01;21(2):145-154. (PMID: 32841585); Pharmacogenomics. 2011 Nov;12(11):1525-33. (PMID: 21902500); Pain Physician. 2019 Jul;22(4):331-340. (PMID: 31337162); Basic Clin Pharmacol Toxicol. 2024 Mar;134(3):333-344. (PMID: 38124280); PLoS Genet. 2016 Mar 24;12(3):e1005910. (PMID: 27010727); Clin Pharmacol Ther. 2010 Sep;88(3):383-9. (PMID: 20668445); J Clin Psychopharmacol. 2011 Aug;31(4):463-9. (PMID: 21694616); Biochem Pharmacol. 2024 Nov;229:116515. (PMID: 39218044); J Neurosci. 2024 Feb 7;44(6):. (PMID: 38124015) |
| Contributed Indexing: | Keywords: CYP2B6; Methadone maintenance treatment; OPRM1; opioid use disorder; pharmacogenetics; serum methadone concentration |
| Entry Date(s): | Date Created: 20251107 Date Completed: 20251107 Latest Revision: 20251109 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12588057 |
| DOI: | 10.2478/bjmg-2025-0010 |
| PMID: | 41200574 |
| Database: | MEDLINE |
Journal Article