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白细胞介素-10(IL-10)基因变异对肾移植后患者免疫抑制治疗效果的影响。

The effect of genetic variations for interleukin-10 (IL-10) on the efficacy of immunosuppressive therapy in patients after kidney transplantation.

机构信息

Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, 60-630 Poznan, Poland; Department of Histocompatibility with Laboratory of Genetic Diagnostics, Regional Blood Center, 60-354 Poznan, Poland.

Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, 60-630 Poznan, Poland.

出版信息

Int Immunopharmacol. 2020 Dec;89(Pt A):107059. doi: 10.1016/j.intimp.2020.107059. Epub 2020 Oct 8.

DOI:10.1016/j.intimp.2020.107059
PMID:33039969
Abstract

Kidney transplantation is the target method of treating chronic kidney disorders. It improves the comfort of patient life by eliminating the need for repeated dialysis. The aim of the study was to examine the correlation between tacrolimus (TAC) dose and genetic variation for interleukin-10 (IL-10) and its effect on the therapeutic outcome. In addition, the correlations between the IL-10 polymorphism andthe clinical and the biochemical parameters of TAC patients were also analyzed. The study included 209 subjects after kidney transplantation, who received TAC every 12 and 24 h. Drug concentrations in blood, selected morphological and biochemical parameters, and the genetic variation of IL-10 (-1082A > G) which may affect immunosuppressant dosage and risk of acute graft rejection were analyzed. Genetic analyses were performed using real-time PCR. No significant correlations between the clinical and the biochemical parameters and IL-10-1082A > G polymorphism for patients receiving TAC after kidney transplantation were found. The analysis of the correlation between TAC dose and IL-10 genetic variation for the -1082A > G polymorphism revealed that patients with the AA genotype required lower immunosuppressive drug doses (AA: 3.54 ± 2.38 mg/day vs AG: 6.18 ± 5.10 mg/day, GG: 4.44 ± 3.01 mg/day). Furthermore, frequencies of the genotypes for the IL-10 -1082A > G polymorphism were characterized by a significantly higher frequency of the AA genotype among TAC 24 as compared to TAC 12 patients. The results of the study indicated that the IL-10 -1082A > G polymorphism may in fact influence the TAC dose. The biochemical parameters of the renal profile in relation to the IL-10 genetic variations were not indicative of higher risk of acute rejection after transplantation.

摘要

肾移植是治疗慢性肾脏疾病的目标方法。它通过消除对反复透析的需求,提高了患者生活的舒适度。本研究旨在探讨他克莫司(TAC)剂量与白细胞介素-10(IL-10)的遗传变异之间的相关性及其对治疗结果的影响。此外,还分析了 IL-10 多态性与 TAC 患者的临床和生化参数之间的相关性。本研究纳入了 209 例肾移植后患者,他们每 12 小时和 24 小时接受一次 TAC。分析了血液中的药物浓度、选定的形态和生化参数以及可能影响免疫抑制剂剂量和急性移植物排斥风险的 IL-10(-1082A>G)遗传变异。使用实时 PCR 进行基因分析。未发现接受肾移植后 TAC 治疗的患者的临床和生化参数与 IL-10-1082A>G 多态性之间存在显著相关性。TAC 剂量与 IL-10 遗传变异之间相关性的分析表明,AA 基因型患者需要较低的免疫抑制药物剂量(AA:3.54±2.38mg/天,AG:6.18±5.10mg/天,GG:4.44±3.01mg/天)。此外,IL-10-1082A>G 多态性的基因型频率特征是,与 TAC 12 患者相比,TAC 24 患者的 AA 基因型频率显著更高。研究结果表明,IL-10-1082A>G 多态性实际上可能影响 TAC 剂量。与 IL-10 遗传变异相关的肾谱生化参数并未提示移植后急性排斥反应的风险增加。

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