Ge J, Wang J, Zhao H, Li K, Jing Y, Li G
Department of Breast Surgery and Key Laboratory of Breast Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China.
Basic Medical College, Tianjin Medical University, Tianjin, P. R. China.
Transplant Proc. 2016 Jul-Aug;48(6):1962-7. doi: 10.1016/j.transproceed.2016.04.016.
Tacrolimus is an immunosuppressive medication for organ transplantation. FOXP3(+) T regulatory cells (Tregs) play roles in suppression of rejection and induction of graft tolerance. This study aimed to evaluate the correlation between the polymorphism of FOXP3 and the blood level of tacrolimus in renal transplant recipients.
This retrospective study included 100 renal transplant recipients receiving tacrolimus treatment and 100 healthy control subjects. Genotyping for FOXP3 rs3761547 AA, AG, GG, rs3761548 AA, AC, CC and rs223236 AA, AG, GG was performed. Concentrations of tacrolimus, creatinine, and urea nitrogen levels in blood were measured.
Frequencies of genotypes of FOXP3 rs3761548 AA, AC, and CC, rs3761547 AA, AG, GG and rs 223236 AA, AG, GG in renal transplant recipients were similar to those in normal people. The blood level of tacrolimus in recipients with rs3761548 CC was significantly higher than that in recipients with rs3761548 AA and AC (P < .001). No difference in the blood level of tacrolimus was found in recipients with different genotypes of rs3761547 and rs223236. Compared to rs3761548 AA and AC groups, there was no difference of Modification of Diet in Renal Disease (MDRD) glomerular filtration rate and the level of blood urea nitrogen before transplantation; however, these 2 parameters were significantly improved after transplantation in the rs3761548 CC group. The level of tacrolimus was correlated positively with MDRD glomerular filtration rate and negatively with the blood urea nitrogen level in recipients with rs3761548 CC genotype after transplantation.
Our study identified a new relationship between FOXP3 rs3761548 and the blood level of tacrolimus. These results suggest that the polymorphism of FOXP3 may affect tacrolimus pharmacokinetics.
他克莫司是一种用于器官移植的免疫抑制药物。FOXP3(+)调节性T细胞（Tregs）在抑制排斥反应和诱导移植耐受中发挥作用。本研究旨在评估肾移植受者中FOXP3基因多态性与他克莫司血药浓度之间的相关性。
这项回顾性研究纳入了100例接受他克莫司治疗的肾移植受者和100例健康对照者。对FOXP3 rs3761547的AA、AG、GG基因型，rs3761548的AA、AC、CC基因型以及rs223236的AA、AG、GG基因型进行基因分型。测定血液中他克莫司、肌酐和尿素氮的浓度。
肾移植受者中FOXP3 rs3761548的AA、AC和CC基因型，rs3761547的AA、AG、GG基因型以及rs223236的AA、AG、GG基因型的频率与正常人相似。rs3761548 CC基因型受者的他克莫司血药浓度显著高于rs3761548 AA和AC基因型受者（P <.001）。rs3761547和rs223生236不同基因型受者的他克莫司血药浓度未发现差异。与rs3761548 AA和AC组相比，移植前肾病饮食改良（MDRD）肾小球滤过率和血尿素氮水平无差异；然而，rs3761548 CC组移植后这两个参数显著改善。移植后rs3761548 CC基因型受者的他克莫司水平与MDRD肾小球滤过率呈正相关，与血尿素氮水平呈负相关。
我们的研究发现了FOXP3 rs3761548与他克莫司血药浓度之间的新关系。这些结果表明，FOXP3基因多态性可能影响他克莫司的药代动力学。
