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学科主题: 基础医学
题名:
Polymorphisms of tumor necrosis factor-alpha, interleukin-10, cytochrome P450 3A5 and ABCB1 in Chinese liver transplant patients treated with immunosuppressant tacrolimus
作者: Li, Dan; Zhu, Ji-Ye; Gao, Jie; Wang, Xin; Lou, Ya-Qing; Zhang, Guo-Liang
关键词: TNF-alpha ; IL-10 ; CYP3A5 ; polymorphism ; liver transplantation ; immunosuppressant therapy
CLINICA CHIMICA ACTA
发表日期: 2007-08-01
DOI: 10.1016/j.cca.2007.05.008
卷: 383, 期:1-2, 页:133-139
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medical Laboratory Technology
研究领域[WOS]: Medical Laboratory Technology
关键词[WOS]: B-VIRUS INFECTION ; CYTOKINE GENE POLYMORPHISMS ; GENOTYPE-PHENOTYPE ASSOCIATIONS ; PROMOTER POLYMORPHISMS ; TNF-ALPHA ; DOSE REQUIREMENTS ; HUMAN HEPATOCYTES ; GRAFT-REJECTION ; PRIMARY CULTURE ; IN-VIVO
英文摘要:

Background: Cytokine production in the host immune response after transplantation may contribute to the variable CYP3A-dependent drug disposition. We investigated the effect of TNF-alpha, IL-10, CYP3A5 and ABCB1 polymorphisms on immunosuppressant tacrolimus pharmacokinetics in liver transplant patients.

Methods: Genetic polymorphisms in TNF-alpha, IL-10, CYP3A5 and ABCB1 were studied in 70 liver transplant recipients and 70 donors. Tacrolimus dosage and blood concentration were investigated at 1, 2 and 3weeks after transplantation.

Results: The IL-10 G-1082A polymorphism in recipients was significantly associated with tacrolimus concentration/dose (C/D) ratios (IL-101082GG < GA < AA) within the first 3weeks posttransplantation (P < 0.05). Recipients with the capacity for low IL-10 production (-1082AA) carrying CYP3A5 non-expressor (CYP3A5*3/*3) liver had the highest C/D ratios (mean: 172.4, 161.7, 160.3 for 1, 2 and 3weeks posttransplantation, respectively); whereas recipients with intermediate or high production of IL-10 (-1082GA or GG) engrafted with CYP3A5 expresser (CYP3A5*1 carrier) liver were found to have the lowest ratios (96.4, 78.0 and 75.4, respectively, P < 0.01).

Conclusions: The IL-10 G-1082A and CYP3A5*3 polyrnorphisms may influence the interindividual variability of tacrolimus pharmacokinetics in Chinese liver transplant patients. This finding provided a new interpretation for the variable immunosuprressant disposition after transplantation. (C) 2007 Elsevier B.V. All rights reserved.

语种: 英语
WOS记录号: WOS:000248465400017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66791
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Beijing Univ, Basic Med Sch, Dept Pharmacol, Beijing 100083, Peoples R China
2.Beijing Univ, Peoples Hosp, Liver Transplantat Ctr, Beijing 100083, Peoples R China

Recommended Citation:
Li, Dan,Zhu, Ji-Ye,Gao, Jie,et al. Polymorphisms of tumor necrosis factor-alpha, interleukin-10, cytochrome P450 3A5 and ABCB1 in Chinese liver transplant patients treated with immunosuppressant tacrolimus[J]. CLINICA CHIMICA ACTA,2007,383(1-2):133-139.
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