Pharmacogenomics study in a Taiwanese 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 on CYP2B6 were associated with plasma S-methadone concentration; SNPs on CYP3A4 were associated with withdrawal symptoms and side effects; and SNPs on CYP2C19 were 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 on OPRM1 were 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.

GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence

“…The methadone dose did not show correlations with the total COWS score >5 (Spearman correlation coefficient, n=23, r=0.34, P= .12 in MMT patients). The clinical characteristics and single gene observations from this cohort were well characterized for the recruitment and treatment responses in our previous studies ( Wang et al, 2013a ).…”

“…In addition, the study was a cross-sectional design. However, participants in the study were recruited from a well-characterized, steady-state MMT cohort ( Wang et al, 2013a ). Medication compliance issues were well controlled by recruiting only subjects who had continuously undergone the MMT and shown regular attendance at the clinic.…”

“…All methods in this study were performed in accordance with the guidelines and regulations of the institutional review committees. The study protocol was approved by the institutional review boards of the National Health Research Institutes (EC0970504, Zhunan, Taiwan) and the 7 participating hospitals: Tao-Yuan Mental Hospital, En-Chu-Kong Hospital, Far-Eastern Memorial Hospital, Taipei City Hospital Song-De and Yang-Ming Branches, China Medical University Hospital, and Wei-Gong Memorial Hospital ( Wang et al, 2013a ). Written informed consent was obtained from all participants.…”

Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study

“…In their 2018 review, Fonseca and Torrens highlighted the influence of CYP2B6 , and to some extent CYP2D6 and CYP2C19 , genetic variability on methadone pharmacokinetics . Three studies described in that review reported that the CYP2B6 gene had no influence on the methadone response.…”

Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use

“…This study was approved by the institutional review boards of the National Health Research Institutes (EC0970504, Zhunan, Taiwan) and the seven participating hospitals [21]. All participants had singed the informed consent.…”