CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation
CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation
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DOI：
10.1093/ndt/gfr253
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发表时间：
2011-09-01
影响因子：
6.1
通讯作者：
Cauffiez, Christelle
中科院分区：
文献类型：
--
作者：
Glowacki, Francois;Lionet, Arnaud;Cauffiez, Christelle
背景。在209例肾移植患者的供体和受体DNA样本中，研究了可能相关的基因多态性CYP3A5 6986A>G和ABCB1 3435C>T对他克莫司药代动力学和移植临床结果的影响。方法/主要结果。平均随访时间为21.8±9个月。他克莫司剂量、谷血浓度（C0）和C0/剂量比仅与受体CYP3A5基因型相关。CYP3A5和ABCB1基因型似乎对活检证实的急性排斥反应和移植功能延迟的发生率没有影响。CYP3A5和ABCB1基因型不影响肾功能。活检的组织学评估也显示他克莫司毒性特征与供体或受体CYP3A5和ABCB1多态性之间没有显著关联。他克莫司节约似乎与CYP3A5和ABCB1基因型无关。受体CYP3A5 6986A>G多态性部分解释了他克莫司药代动力学的个体间差异。2年随访的临床结果似乎与供体或受体CYP3A5 6986A>G和/或ABCB1 3435C>T多态性无关。
Background. The effect of potentially relevant genetic polymorphisms, CYP3A5 6986A>G and ABCB1 3435C>T, on Tacrolimus pharmacokinetics and graft clinical outcome was investigated in donor and recipient DNA samples from 209 kidney transplant patients.Methodology/principal findings. The mean follow-up was 21.8 +/- 9 months. The Tacrolimus dose, trough blood concentrations (C0) and C0/dose ratio were only statistically correlated with the recipient CYP3A5 genotype. CYP3A5 and ABCB1 genotypes appeared to have no influence on the incidence of Biopsy Proven Acute Rejection and Delayed Graft Function. Renal function was not affected by CYP3A5 and ABCB1 genotypes. Histological evaluation of biopsies revealed also no significant association between Tacrolimus toxicity features and donor or recipient CYP3A5 and ABCB1 polymorphisms. Tacrolimus sparing appeared to be independent of CYP3A5 and ABCB1 genotypes.Conclusions/significance. Recipient CYP3A5 6986A>G polymorphism explains part of the interindividual variability of the pharmacokinetics of Tacrolimus. The clinical outcome at 2-year follow-up does not appear to be related to the donor or recipient CYP3A5 6986A>G and/or ABCB1 3435C>T polymorphisms.