國家衛生研究院 NHRI:Item 3990099045/5742
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5742


    Title: The genetic polymorphisms in ALDH2 influence the methadone dose and adverse reactions in patients with heroin addiction
    Authors: Tian, JN;Wang, SC;Chen, CH;Tsou, HH;Ho, IK;Chan, HW;Fang, CP;Hsiao, CF;Tan, HKL;Lin, LN;Wu, CS;Su, LW;Huang, CL;Yang, YH;Wu, JY;Lin, KM;Chen, CY;Liu, SC;Liu, YL
    Contributors: Division of Mental Health and Addiction Medicine;Division of Biostatistics and Bioinformatics
    Abstract: Heroin addicts often combine the use of alcohol as multiple drug abusers. ¬e use of alcohol may create hepatic toxicity, increase the severity of withdrawal and side e ects, and cause di culty in methadone-dosage regimen while under the treatment. To decipher the role of the alcohol-elimination process in these patients under methadone treatment, this study was designed to test the hypothesis of whether the alcohol metabolic gene, aldehyde dehydrogenase (ALDH2), could be indicators of methadone treatment dose, plasma concentration, side e ects, and withdrawal symptoms. ¬is study may provide insights in dealing with heroin addiction combined with alcohol users. ¬is study recruited a total of 366 heroin addicts who had taken methadone for at least 3 months and continued to take the medicine in the past 5 days before being enrolled in the study. ¬eir steady-state plasma methadone and metabolite 2-ethylidene- 1,5-dime-thyl-3,3-diphenylpyrrolidine (EDDP) were measured by high-performance liquid chromatography. ¬e selected single-nucleotide polymorphisms (SNPs) of ALDH2 were also genotyped on those patients. We found that the ALDH2 SNPs of rs4648328 (intron 3), rs441 (intron 6), rs4646778 (intron 9), and rs671 (exon 12) genotypes were signi cantly associated with methadone dose (GLM, P<0.031, power>0.80). ¬e rs671 also showed an association with the heart-rate–corrected QT (QTc) change in electrocardiogram (ECG) (allele-type permutation, P = 0.039, power = 0.52), where the alcohol fast metabolizer of G-allele carrier showed higher QTc change than the A-allele carrier. ¬e SNPs of rs4767944 (intron 1), rs10849970 (intron 4), and rs4767035 (intron 11) genotypes were associated with withdrawal symptoms of runny nose or tearing (permutation, P < 0.0067, power>0.82) in patients claiming to have been drinking alcohol. ¬e SNP of the rs4767035 allele type was associated with the Treatment Emergent Symptoms Scale (TESS) of weight gain (permutation, P = 0.0039, power = 0.85) in patients who did not claim to have been drinking alcohol. In summary, the SNPs of ALDH2 may be indicators for not only methadone dosage regimen, but also withdrawal symptoms and side e ects.
    Date: 2011-05
    Relation: Drug Metabolism Reviews. 2011 May;43(Suppl.1):26.
    Link to: http://dx.doi.org/10.3109/03602532.2011.567807
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0360-2532&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000289629400049
    Appears in Collections:[Yu-Li Liu] Conference Papers/Meeting Abstract
    [Keh-Ming Lin(2004-2009)] Conference Papers/Meeting Abstract
    [Chia-Hsiang Chen(2009-2013)] Conference Papers/Meeting Abstract
    [Ing-Kang Ho(2006-2011)] Conference Papers/Meeting Abstract
    [Sheng-Chang Wang] Conference Papers/Meeting Abstract
    [Chin-Fu Hsiao] Conference Papers/Meeting Abstract
    [Hsiao-Hui Sophie Tsou] Conference Papers/Meeting Abstract

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