國家衛生研究院 NHRI:Item 3990099045/6876
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6876


    Title: OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: A cross sectional study
    Authors: Chen, YT;Tsou, HH;Kuo, HW;Fang, CP;Wang, SC;Ho, IK;Chang, YS;Chen, CH;Hsiao, CF;Wu, HY;Lin, KM;Chen, ACH;Tsai-Wu, JJ;Liu, YL
    Contributors: Division of Mental Health and Addiction Medicine;Division of Biostatistics and Bioinformatics
    Abstract: Majority of the heroin-dependent patients smoke cigarettes. Although it has been reported that the OPRM1 genetic polymorphism is associated with the brain mu-opioid receptor binding potential in cigarette smokers, there is no direct evidence showing the impact of plasma cotinine, a nicotine metabolite, on treatment responses to methadone maintenance treatment (MMT). In this study, we aimed to test the hypothesis that the genetic polymorphisms in the OPRM1 are associated with the methadone treatment responses and the severity of cigarette smoking directly measured by the plasma concentration of cotinine in a Taiwanese MMT cohort. Fifteen OPRM1 single-nucleotide polymorphisms (SNPs) were selected and genotyped on DNA samples of 366 MMT patients. Plasma concentrations of cotinine were measured by cotinine enzyme-linked immunosorbent assay. The plasma cotinine concentration had positive correlation with concentrations of methadone (P=0.042) and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (P=0.037). Methadone treatment non-responders, defined by a positive urine morphine test, had a higher plasma concentration of cotinine (P=0.005), but a lower plasma concentration-to-dose ratio of both R- and S-methadone (P=0.001 and 0.012, respectively) than the responders. OPRM1 genetic variants, rs1074287, rs6912029, rs1799971, rs12209447, rs510769, rs3798676, rs553202, rs7748401, rs495491, rs10457090, rs589046, rs3778152 and rs563649, were significantly associated with the plasma concentration of cotinine when using recessive model for genotypes (general linear model (GLM), P<0.038; false discovery rate (FDR)<0.035) and additive model for allele types (GLM, P<0.03; FDR<0.049) in association analyses. The G allele carriers of SNP rs1799971 (A118G) on exon 1 of OPRM1 gene had a lower plasma cotinine concentration than the A allele carriers (GLM, P=0.029). OPRM1 genetic polymorphisms are associated with the plasma concentration of cotinine in a Taiwanese MMT cohort. Carriers with the major allele of SNP rs1799971 had a higher plasma cotinine concentration.
    Date: 2013-02
    Relation: Journal of Human Genetics. 2013 Feb;58(2):84-90.
    Link to: http://dx.doi.org/10.1038/jhg.2012.139
    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:000316612200007
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84875440123
    Appears in Collections:[Yu-Li Liu] Periodical Articles
    [Keh-Ming Lin(2004-2009)] Periodical Articles
    [Sheng-Chang Wang] Periodical Articles
    [Ing-Kang Ho(2006-2011)] Periodical Articles
    [Hsiao-Hui Sophie Tsou] Periodical Articles
    [Chin-Fu Hsiao] Periodical Articles

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