Impact of interleukin-10 gene polymorphisms on tacrolimus dosing requirements in Chinese liver transplant patients during the early posttransplantation period
Impact of interleukin-10 gene polymorphisms on tacrolimus dosing requirements in Chinese liver transplant patients during the early posttransplantation period
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DOI：
10.1007/s00228-011-0993-8
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发表时间：
2011-08-01
影响因子：
2.9
通讯作者：
Peng, Zhihai
中科院分区：
文献类型：
--
作者：
Zhang, Xiaoqing;Wang, Zhaowen;Peng, Zhihai
目的药物遗传学具有阐明个体对药物反应差异的遗传基础的潜力。CYP 3A 5和ABCB 1基因多态性对免疫抑制剂他克莫司的影响在先前的肝移植研究中已有报道。肝移植术后早期白细胞介素-10（IL-10）基因表达的功能是复杂的。在这项研究中，我们研究了受体和捐助者的IL-10基因型，以澄清这些遗传变异对他克莫司的剂量要求和药代动力学的影响。方法IL-10，CYP 3A 5，ABCB 1的遗传多态性进行了评估，为53例肝移植受体和53名捐助者。他克莫司剂量和血药浓度在移植后1，2，3周和1个月进行了测定。通过PCR扩增和DNA测序评估IL-10 G-1082 A、C-819 T和C-592 A多态性; CYP 3A 5 A6986 G多态性; ABCB 1 C1236 T、G2677 T和C3435 T多态性。在前2周内，接受CYP 3A 5非表达者和低IL-10产生基因型（-819 TT，-592 AA）供体的受体的他克莫司C/D比值高于接受CYP 3A 5非表达者和高IL-10产生基因型（-819 CC或CT，-592 CC或AC）供体的受体。两组患者的实验室数据及影响他克莫司C/D比值的临床特征差异均无统计学意义（P>0.05）。结论检测供者IL-10和CYP 3A 5基因多态性，可为肝移植术后早期他克莫司给药方案的制定提供个体化依据。
Aim Pharmacogenetics holds the potential to elucidate the inherited basis of differences between individual responses to drugs. Impacts of CYP3A5 and ABCB1 gene polymorphisms on the immunosuppressant tacrolimus have been reported in previous studies of liver transplantation. The functions of interleukin-10 (IL-10) gene expression are complex in the early period after liver transplantation. In this study, we examined the IL-10 genotypes of both recipients and donors to clarify the influence of these genetic variants on tacrolimus dose requirements and pharmacokinetics.Methods Genetic polymorphisms of IL-10, CYP3A5, and ABCB1 were evaluated for 53 liver transplant recipients and 53 donors. Tacrolimus doses and blood concentrations were determined at 1, 2, and 3 weeks, and 1 month after transplantation. IL-10 polymorphisms at G-1082A, C-819 T, and C-592A; CYP3A5 polymorphisms at A6986G; and ABCB1 polymorphisms at C1236T, G2677T, and C3435T were assessed by PCR amplification and DNA sequencing.Results Recipients who received organs from CYP3A5*3/*3 donors had higher tacrolimus C/D ratios. In the first 2 weeks, the tacrolimus C/D ratios of the recipients with donors who were CYP3A5 nonexpressors and had a low IL-10 production genotype (-819TT, -592 AA) were higher than those with donors who were CYP3A5 nonexpressors and had a high IL-10 production genotype (-819CC or CT, -592CC or AC). There were no significant differences in laboratory data or clinical characteristics (which could influence the tacrolimus C/D ratio) between the two groups of patients (P>0.05).Conclusion Determining IL-10 and CYP3A5 polymorphisms of donors may allow individualized tacrolimus dosage regimens to be determined for liver transplant patients during the early posttransplantation period.