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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5741


    Title: Genetic polymorphisms in PXR associated with serum concentration and metabolism to treatment with the antidepressant paroxetine
    Authors: Liu, YL;Lin, KM;Tsou, HH;Tian, JN;Chen, CH;Shen, WW;Lu, SC;Liu, CY;Hsiao, MC;Tang, HS;Liu, SI;Chang, LH;Hsiao, CF;Kuo, HW;Hsu, YT;Liu, SC;Tu, SL
    Contributors: Division of Mental Health and Addiction Medicine;Division of Biostatistics and Bioinformatics
    Abstract: Antidepressant paroxetine is a serotonin reuptake inhibitor used in the treatment of major depressive disorder. Its metabolism is through liver cytochrome P450 (CYP) 3A4, which is regulated by nuclear receptor pregnane X recep-tor (PXR; also known as nuclear receptor subfamily 1, group I, member 2; NR1I2) in its expression and activities. In this study, we tested whether PXR genetic polymorphisms could be markers for the metabolism and treatment e -cacy of paroxetine. We recruited 241 major depressive patients who had taken paroxetine for 8 weeks. eir serum paroxetine and its metabolite (-)trans 4-(4- uorophenyl)-3-(4-hydroxy-3- methoxyphenoxymethyl) piperidine-hydro-chloride (BRL 36610A) concentrations were measured at weeks 2, 4, and 8, and their genomic DNAs were genotyped on 28 single-nucleotide polymorphisms (SNPs) of PXR. All the SNPs were at equilibrium in the Hardy-Weinberg test, except rs6785049, rs3732359, and rs3732360. Four haplotype blocks—block 1 (rs1523130-rs3814055-rs1523127), block 2 (rs1403526-rs1357459- rs6772976-rs2461823-rs13059232-rs6771638-rs2461817), block 3 (rs1464603- rs2472681), and block 4 (rs11917714-rs6785049-rs2276707-rs3732359-rs3732360 -rs6438550-rs3814057-rs3814058)—were com-posed among the SNPs. We found that six SNPs of rs1403526 (P = 0.0071), rs1357459 (P = 0.015), rs6772976 (P = 0.0091), rs2461823 (P = 0.0073), rs13059232 (P = 0.0091), and rs6771638 (P = 0.0094) of allele types in intron 1 of PXR were signi -cantly associated with serum concentrations of paroxetine at week 4. ree SNPs near haplotype block 3 of rs1464603, rs2472681, and rs3732357 in both genotypes (P < 0.023) and allele types (P < 0.008) were signi cantly associated with the metabolic ratio of BRL36610A/paroxetine at week 2. Four SNPs in either intron 1 of rs1357459, rs6771638, and rs2461817 or exon 9 of rs6438550 showed marginally signi cant associations with remission response at week 4 (P < 0.044). No haplotype blocks showed any signi cant association with paroxetine concentration, metabolism, or treatment response. us, PXR loci may be indicators for the concentrations or metabolic ratios of paroxetine and, to a lesser extent, with remission response.
    Date: 2011-05
    Relation: Drug Metabolism Reviews. 2011 May;43(Suppl.1):71.
    Link to: http://dx.doi.org/10.3109/03602532.2011.567811
    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:000289629400129
    Appears in Collections:[林克明(2004-2009)] 會議論文/會議摘要
    [劉玉麗] 會議論文/會議摘要
    [蕭金福] 會議論文/會議摘要
    [鄒小蕙] 會議論文/會議摘要

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