title: Pharmacogenomics study in a Taiwan methadone maintenance cohort.
abstract: Pharmacogenomics is research to study the drug treatment responses in subgroups of patients according to their genetic variants or genetic expression information. Methadone maintenance treatment, which is usually prescribed for patients with heroin dependence, was launched in Taiwan by the government in 2006. In this study, 366 patients who had taken methadone continually in the previous 7 days were examined. Data from administration of the Treatment Outcomes Profile (TOP), Severity of Dependence Scale (SDS), Clinical Opioid Withdrawal Scale (COWS), and Treatment Emergent Symptoms Scale (TESS) were obtained from patients' report records. Genes encoding the liver cytochrome P-450 (CYP) enzymes that are involved with the metabolism of methadone (CYP2B6, 3A4 and 2C19) were selected and genotyped in this cohort. We found that the SNPs onCYP2B6were associated with plasmaS-methadone concentration; SNPs onCYP3A4were associated with withdrawal symptoms and side effects; and SNPs onCYP2C19were associated with methadone dose. SNPs in the genes encoding the morphine phase II metabolic enzyme,UGT2B7, were associated with withdrawal symptom scores. In pharmacodynamic genes, the SNPs onOPRM1were associated with insomnia and change in libido side effects. We conclude that SNP markers may be useful for future methadone dosage adjustment and to reduce adverse reactions.
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Sheng-Chang
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Tsou
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan ; Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Ing-Kang
authors.initials: IK
authors.lastname: Ho
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Keh-Ming
authors.initials: KM
authors.lastname: Lin
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan ; Department of Psychiatry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
keywords: COWS; CYP2B6; TESS; methadone; opioid receptors; pharmacogenomics