國家衛生研究院 NHRI:Item 3990099045/13997
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13997


    Title: Association of the D-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment
    Authors: Liu, TH;Tsou, HH;Chung, RH;Liu, SC;Wang, SC;Kuo, HW;Fang, CP;Chen, ACH;Liu, YL
    Contributors: Center for Neuropsychiatric Research;Institute of Population Health Sciences
    Abstract: Methadone is a synthetic opioid used for the maintenance treatment (MMT) of heroin dependence. It primarily binds to the mu-opioid receptor (MOR; with its gene, namely OPRM1). Methadone is also an N-methyl-D-aspartate (NMDA) receptor antagonist. The role of NMDA receptor in the regulatory mechanisms of methadone dosage in heroin dependent patients is so far not clear. D-amino acid oxidase (DAO) is an important enzyme that indirectly activates the NMDA receptor through its effect on the D-serine level. To test the hypothesis that genetic polymorphisms in the DAO gene are associated with methadone treatment dose and responses, we selected four single nucleotide polymorphisms (SNPs) in DAO from the literature reports of the Taiwanese population. SNPs were genotyped in 344 MMT patients. In this study, we identified a functional SNP rs55944529 in the DAO gene that reveals a modest but significant association with the methadone dosage in the recessive model of analysis (P = 0.003) and plasma concentrations (P = 0.003) in MMT patients. However, it did not show association with plasma methadone concentration in multiple linear regression analysis. It is also associated with the methadone adverse reactions of dry mouth (P = 0.002), difficulty with urination (P = 0.0003) in the dominant model, and the withdrawal symptoms of yawning (P = 0.005) and gooseflesh skin (P = 0.004) in the recessive model. Our results suggest a role of the indirect regulatory mechanisms of the NMDA reporter, possibly via the DAO genetic variants, in the methadone dose and some adverse reactions in MMT patients.
    Date: 2022-05
    Relation: Journal of Human Genetics. 2022 May;67(5):273-278.
    Link to: http://dx.doi.org/10.1038/s10038-021-01008-7
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1434-5161&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000738423200001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85122245790
    Appears in Collections:[Yu-Li Liu] Periodical Articles
    [Sheng-Chang Wang] Periodical Articles
    [Ren-Hua Chung] Periodical Articles
    [Hsiao-Hui Sophie Tsou] Periodical Articles

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