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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 volume 65, pages 381–386 (2020)Cite this article

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Abstract

Delta opioid receptor (DOR) is well known to be involved in heroin dependence. This study tested the hypothesis that single nucleotide polymorphisms (SNPs) in the opioid receptor delta 1 (OPRD1) gene coding region are associated with treatment responses in a methadone maintenance therapy (MMT) cohort in Taiwan. Three hundred forty-four MMT patients were recruited. Diastolic/systolic blood pressure, heart rate, methadone dosage, and plasma concentrations of methadone were recorded. Twenty-five SNPs located within the OPRD1 genetic region were selected and genotyped from the genomic DNA of all 344 participants. After pairwise tagger analyses, tagger SNP rs204047 showed a significant association with methadone dosage (P = 0.0019), and tagger SNPs rs204047 and rs797397 were significantly associated with plasma R, S-methadone concentrations (P < 0.0006) in patients tested negative in the urine morphine test, which indicated patients with a better response to MMT. The major genotype carriers showed a higher methadone dosage and higher plasma concentrations of R, S-methadone than the minor genotype carriers. The results indicated that OPRD1 genetic variants were associated with methadone dosage and methadone plasma concentration in MMT patients with a negative morphine test result.

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Acknowledgements

We thank Ming-Chu Tseng, Pei-Fang Li, Shu-Chuan Ting, Yu-Ching Lin, Miao-Fang Lee, Chi-Yun Huang, and Yu-Hun Tsai of the nursing staff from the six participating hospitals for interviewing the patients. We also thank the Clinical Trial Information Management System (CTIMeS) at NHRI for the data collection. We thank the National Center for Genome Medicine at Academia Sinica, Taiwan, for genotyping/technical support. This Center was supported by grants from the National Core Facility Program for Biotechnology of National Science Council, Taiwan. We also acknowledge the significant contributions of the 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. 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), Ministry of Science and Technology (MOST 106-2320-B-400-012), and National Health Research Institutes, Taiwan (NP-107-PP-06, NP-108-PP-06, NP-107-SP-04, and NP-108-SP-04).

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  1. These authors contributed equally: Chiu-Ping Fang, Sheng-Chang Wang

Authors and Affiliations

  1. Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan

    Chiu-Ping Fang, Sheng-Chang Wang, Shu Chih Liu, Hsiang-Wei Kuo, Tung-Hsia Liu & Yu-Li Liu

  2. Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan

    Hsiao-Hui Tsou, Ren-Hua Chung & Ya-Ting Hsu

  3. Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung, Taiwan

    Hsiao-Hui Tsou

  4. Department of Psychiatry, the Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA

    Andrew C. H. Chen

  5. The Feinstein Institute for Medical Research, Hofstra Northwell School of Medicine at Hofstra University, Manhasset, NY, USA

    Andrew C. H. Chen

  6. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan

    Yu-Li Liu

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Fang, CP., Wang, SC., Tsou, HH. et al. Genetic polymorphisms in the opioid receptor delta 1 (OPRD1) gene are associated with methadone dose in methadone maintenance treatment for heroin dependence. J Hum Genet 65, 381–386 (2020). https://doi.org/10.1038/s10038-019-0718-x

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