Abstract
Aim:
To evaluate the effects of UDP-glucuronosyltransferases (UGTs) polymorphisms on the pharmacokinetics of the immunosuppressant mycophenolate mofetil (MMF) in Chinese renal transplant recipients.
Methods:
A total of 127 renal transplant patients receiving MMF were genotyped for polymorphisms in UGT1A9 −1818T>C, I399C>T, −118T9/10, −440C>T, −331T>C, UGT2B7 IVS1+985A>G, 211G>T, −900A>G, UGT1A8 518C>G and UGT1A7 622T>C. The plasma concentrations of the MMF active moiety mycophenolic acid (MPA) and main metabolite 7-O-MPA-glucuronide (MPAG) were analyzed using HPLC. Univariate and multivariate analyses were used to assess the effects of UGT-related gene polymorphisms on MPA pharmacokinetics.
Results:
The dose-adjusted MPA AUC0–12 h of the patients with the UGT2B7 IVS1+985AG genotype was 48% higher than that of the patients with the IVS1+985AA genotype, which could explain 11.2% of the inter-individual variation in MPA pharmacokinetics. The dose-adjusted MPAG AUC0–12 h of the patients with the UGT1A7 622CC and UGT1A9 −440CT/−331TC genotypes, respectively, was significantly higher than that of the patients with 622T homozygotes and −440C/−331T homozygotes. Furthermore, the genotypes UGT1A9 −1818T>C and UGT1A8 518C>G were associated with a low dose-adjusted MPAG AUC0–12 h.
Conclusion:
The UGT2B7 11+985A>G genotype is associated with the pharmacokinetics of MPA in Chinese renal transplant patients, which demonstrates the usefulness of this SNP for individualizing MMF dosing.
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Acknowledgements
We appreciate the financial support provided by the National Major Projects for Science and Technology Development from Science and Technology Ministry of China (Grant No 2012ZX09506001-004), the National Natural Science Foundations of China (No 81102515, 81320108027 and 81173131), the Key Laboratory Foundation of Guangdong Province (No 2011A060901014) and the Major Scientific and Technological Project of Guangdong Province (No 2011A080300001 and 2012A080202013).
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Xie, Xc., Li, J., Wang, Hy. et al. Associations of UDP-glucuronosyltransferases polymorphisms with mycophenolate mofetil pharmacokinetics in Chinese renal transplant patients. Acta Pharmacol Sin 36, 644–650 (2015). https://doi.org/10.1038/aps.2015.7
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DOI: https://doi.org/10.1038/aps.2015.7
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