國家衛生研究院 NHRI:Item 3990099045/7537
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7537


    Title: Functional genetic polymorphisms in CYP2C19 Gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort
    Authors: Wang, SC;Ho, IK;Tsou, HH;Liu, SW;Hsiao, CF;Chen, CH;Tan, HK;Lin, L;Wu, CS;Su, LW;Huang, CL;Yang, YH;Liu, ML;Lin, KM;Liu, SC;Wu, HY;Kuo, HW;Chen, AC;Chang, YS;Liu, YL
    Contributors: Center for Neuropsychiatric Research;Division of Biostatistics and Bioinformatics;Division of Clinical Trial Statistics
    Abstract: Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.
    Date: 2013-09
    Relation: OMICS :A Journal of Integrative Biology. 2013 Sep;17(10):519-526.
    Link to: http://dx.doi.org/10.1089/omi.2012.0068
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1536-2310&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000324834200004
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84884797577
    Appears in Collections:[Yu-Li Liu] Periodical Articles
    [Keh-Ming Lin(2004-2009)] Periodical Articles
    [Ing-Kang Ho(2006-2011)] Periodical Articles
    [Sheng-Chang Wang] Periodical Articles
    [Chin-Fu Hsiao] Periodical Articles
    [Hsiao-Hui Sophie Tsou] Periodical Articles

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