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Abstract
Aim: Methadone dose is related to treatment success in individuals under methadone maintenance treatment (MMT). We constructed a gene matrix using previously identified genetic polymorphisms in CYP450 and determined their genetic influence on methadone dose or tolerance. Materials & methods: The allelic combinations of CYP450 genetic variants (two from CYP2C19, four from CYP2B6 and five from CYP3A4) were analyzed in 366 MMT heroin dependent patients as possible determinants of methadone dose and tolerance using analysis of covariance. Results: Methadone dose (p = 0.007) and tolerance (p = 0.06) were mainly influenced by CYP2C19 gene dose. Moreover, dominant influence of the CYP2C19 gene dose on methadone dose and tolerance was only found among MMT patients with negative urine morphine test results, but not among those with positive results. Conclusion: The findings suggest that CYP2C19 gene dose may serve as a potential indicator for assessing methadone dose and tolerance in MMT patients.
Original submitted 5 September 2013; Revision submitted 23 January 2014
Acknowledgements
The authors thank the physicians and nursing staff from the six participating hospitals, and S-Y Chou, Y-F Lin, K-C Fang, C-L Huang, L-W Su, Y-C Fang, M-L Liu, M-C Tseng, P-F Li, S-C Ting, Y-C Lin, M-F Lee, C-Y Huang and Y-H Tsai for conducting recruitment and interviewing patients. The authors thank T Bartell for English editing. The authors also thank Y-H Shih for assistance with preparing the manuscript, and the Clinical Trial Information Management (CTIMeS) team at NHRI for data collection. The authors also acknowledge the significant contributions of the Tao-yuan Psychiatric Center, En-Chu-Kong Hospital, Far-Eastern Memorial Hospital, Taipei City Hospital Song-De Campus, China Medical University and Hospital, and Taipei City Hospital Yang-Ming Campus.
Financial & competing interest disclosure
This study was supported by grants from the National Research Program for Genomic Medicine (NSC 98-3112-B-400-011, NSC 99-3112-B-400-003 and NSC 100-3112-B-400-015), the National Science Council (NSC 97-2314-B-400-001-MY3 and NSC 100-2314-B-400-002-MY3) and the National Health Research Institutes, Taiwan (PH-098-PP-41, PH-098-PP-46, PH-098-PP-38, PH-098-PP-36, PH-098, 99-PP-42, PH-099,100-PP-37, PH-101-PP-32, NP-102-PP-04, PH-98, 99, 100-SP-11, PH-101-SP-03, NP-102-SP-04 and NHRI-101, 102A1-PDCO-1312141). H-J Tsai is supported in part by grants from the National Health Research Institutes, Taiwan (PH-099-PP-56, PH-102-PP-14, PH-101-SP-14 and PH-102-SP-05). The authors thank the National Center for Genome Medicine at Academia Sinica, Taiwan, for genotyping/technical support. This Center is supported by grants from the National Core Facility Program for Biotechnology of the National Science Council, Taiwan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.