The associations of IL-18 serum levels and promoter polymorphism with tacrolimus pharmacokinetics and hepatic allograft dysfunction in Chinese liver transplantation recipients
The associations of IL-18 serum levels and promoter polymorphism with tacrolimus pharmacokinetics and hepatic allograft dysfunction in Chinese liver transplantation recipients
复制标题
中国肝移植受者血清IL-18水平和启动子多态性与他克莫司药代动力学和同种异体肝功能障碍的关系
DOI：
10.1016/j.gene.2011.10.008
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发表时间：
2012-01-10
期刊：
影响因子：
3.5
通讯作者：
Wang, Lanlan
中科院分区：
文献类型：
--
作者：
Li, Yi;Zou, Yuangao;Wang, Lanlan
白细胞介素18（IL-18）是一种有效的促炎细胞因子，其促进TNF-α、IL-1 β、IL-2和IFN-γ的分泌。这些炎性细胞因子均能影响CYP 450和MDR依赖的药物处置。另一方面，这些细胞因子可诱导移植肝功能障碍。我们研究了肝移植受者血清IL-18和IL-18基因启动子多态性对他克莫司药代动力学和肝移植功能障碍的影响。共有155例肝移植受者入组本研究（34例女性和121例男性）。术后随访16-96个月，平均52个月，移植肝功能障碍14例，无移植肝功能障碍141例。采用高分辨熔解曲线分析法（HRM）对IL-18基因启动子区G-137 C（rs 187238）和A-607 C（rs 1946518）两个单核苷酸多态性位点进行了研究。同时观察他克莫司剂量、血药浓度、血清IL-18和IFN-γ水平。我们发现，血清IL-18和IFN-γ水平较高的受者他克莫司浓度/剂量（CID）比值较低（P
Interleukin 18 (IL-18) is a potent proinflammatory cytokine, which promotes the secretions of TNF-alpha, IL-1 beta, IL-2 and IFN-gamma. All those inflammatory cytokines can influence the CYP450 and MDR dependent drug disposition. On the other side, those cytokines can induce hepatic allograft dysfunction. We investigated the effects of serum IL-18 and IL-18 gene promoter polymorphisms on tacrolimus pharmacokinetics and hepatic allograft dysfunction in liver transplant recipients. A total of 155 liver transplant recipients were enrolled into this study (34 females and 121 males). The mean follow-up was 52 months (range 16-96 months).The total liver transplant recipients were divided into hepatic allograft dysfunction (N = 14) and no hepatic allograft dysfunction (N = 141). We studied two single-nucleotide polymorphisms in the promoter region of IL-18 gene at the position G-137C (rs187238) and A-607C (rs1946518) by HRM analysis (high-resolution melting curve analysis). Tacrolimus dosage, tacrolimus blood concentration, serum levels of IL-18 and IFN-gamma were also investigated. We found the recipients with higher IL-18 and IFN-gamma serum levels had lower tacrolimus concentration/dose (CID) ratios (P