FOXP3 rs3761548 polymorphism is associated with tacrolimus-induced acute nephrotoxicity in renal transplant patients
FOXP3 rs3761548 polymorphism is associated with tacrolimus-induced acute nephrotoxicity in renal transplant patients
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FOXP3 rs3761548 多态性与肾移植患者他克莫司诱导的急性肾毒性相关
DOI：
10.1007/s00228-016-2140-z
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发表时间：
2017
影响因子：
2.9
通讯作者：
Zhong Mingkang
中科院分区：
文献类型：
--
作者：
Wu Zhuo;Xu Qinxia;Qiu Xiaoyan;Jiao Zheng;Zhang Ming;Zhong Mingkang
目的探讨FOXP3和CCDC22基因多态性对肾移植患者他克莫司（TAC）疗效和安全性的潜在影响。方法对114例经tac维持免疫抑制的肾移植患者进行基因多态性检测，随访2年以上。采用Kaplan-Meier估计和多因素Cox回归分析，研究FOXP3 rs3761547、rs3761548、rs3761549、rs2232365、rs2280883和CCDC22 rs2294021多态性与急性排斥反应、taca诱导的急性肾毒性、肺炎等临床结局的关系。通过线性混合模型评估这些基因多态性对肾小球滤过率随时间变化的影响。结果FOXP3 rs3761548 AA和AC基因型患者发生tac诱导急性肾毒性的风险是CC基因型患者的10倍。在肾移植患者中，我们没有发现其他遗传变异与tac相关结果之间的任何关联。结论在肾移植患者中，tac诱导的急性肾毒性与FOXP3 rs3761548多态性有关。FOXP3 rs3761548可能作为预防TAC毒性的生物标志物，并有助于TAC的个体化治疗。
PurposeThe purpose of this study was to investigate the potential impact of FOXP3 and CCDC22 gene polymorphisms on efficacy and safety of tacrolimus (TAC) in renal transplant patients.MethodsGenetic polymorphisms were detected in 114 Chinese renal transplant patients who were on TAC-based maintenance immunosuppression and were followed up for at least 2 years. The relationships between FOXP3 rs3761547, rs3761548, rs3761549, rs2232365, rs2280883, and CCDC22 rs2294021 polymorphisms and clinical outcomes such as acute rejection, TAC-induced acute nephrotoxicity, and pneumonia were investigated by using Kaplan-Meier estimates and multivariate Cox regression analysis. The influence of these gene polymorphisms on the change in estimated glomerular filtration rate over time was evaluated by linear mixed model.ResultsPatients with FOXP3 rs3761548 AA and AC genotypes had a 10-fold higher risk for TAC-induced acute nephrotoxicity than those with CC genotype. We did not find any association between other genetic variants and TAC-related outcomes in renal transplant patients.ConclusionsOur study demonstrated the TAC-induced acute nephrotoxicity was associated with FOXP3 rs3761548 polymorphism in renal transplant patients. FOXP3 rs3761548 might serve as a biomarker to prevent TAC toxicity and help progression toward individualized therapy of TAC.