Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacology and Pharmacogenomics-CRIFF, Università del Piemonte Orientale 'A. Avogadro', Novara, Italy.
Pharmacogenet Genomics. 2012 Aug;22(8):642-5. doi: 10.1097/FPC.0b013e3283557c74.
In the present study, we performed a systematic review and meta-analysis on published data to examine the impact of CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms on tacrolimus dose-adjusted trough levels (C0/D) and acute rejection rates in adult renal transplant patients. Despite the presence of significant heterogeneity in all comparisons, random-effects model showed significantly higher tacrolimus C0/D in CYP3A53/3 compared with CYP3A51 allele carriers, either in the overall analysis and when stratifying for ethnicity or time of post-transplantation (≤1, 3-6, 12-24 months). In contrast, no consistent evidence of an effect of the ABCB1 3435C>T variant was detected on tacrolimus C0/D, except for a modest effect limited to the first month after renal transplantation. In addition, from the current evidence available, CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms seem to have little or no effect on the acute rejection rates in renal transplant patients under immunosuppressive therapy with tacrolimus.
在本研究中，我们对已发表的数据进行了系统评价和荟萃分析，以研究 CYP3A5 6986A>G 和 ABCB1 3435C>T 多态性对成年肾移植患者他克莫司剂量调整谷浓度（C0/D）和急性排斥反应率的影响。尽管所有比较均存在显著的异质性，但随机效应模型显示，CYP3A53/3 与 CYP3A51 等位基因携带者相比，他克莫司 C0/D 明显更高，无论是在总体分析中，还是在按种族或移植后时间（≤1、3-6、12-24 个月）分层时。相比之下，除了在肾移植后第一个月存在适度影响外，ABCB1 3435C>T 变体对他克莫司 C0/D 没有一致的影响证据。此外，根据目前可用的证据，CYP3A5 6986A>G 和 ABCB1 3435C>T 多态性似乎对接受他克莫司免疫抑制治疗的肾移植患者的急性排斥反应率影响很小或没有影响。
