Influence of UDP-Glucuronosyltransferase Polymorphisms on Mycophenolic Acid Metabolism in Renal Transplant Patients

Abstract

This study aims to evaluate the effects of the UDP-glucuronosyltransferases (UGTs) polymorphisms on mycophenolic acid (MPA) metabolites in renal transplant patients. Total 11 single nucleotide polymorphisms (SNPs) of UGT1A1, UGT1A7, UGT1A8, UGT1A9, UGT1A10 and UGT2B7 were genotyped in 79 renal transplant patients. The associations of SNPs and clinical factors with dose-adjusted MPA area under the plasma concentration-time curve (AUC/D), the dose-adjusted concentration (C0/D) of MPAG and the dose-adjusted plasma concentration (C0/D) of AcMPAG were analyzed. In the univariate analysis, UGT1A1 rs4148323, age and anion gap were associated with MPA AUC/D. MPA AUC/D in patients with the GA genotype of UGT1A1 rs4148323 was higher than that in patients with the GG genotype. UGT1A1 rs4148323, UGT1A9 rs2741049 and clinical factors, including age, serum total bilirubin, adenosine deaminase, anion gap, urea, creatinine, were associated with MPAG C0/D. In addition, UGT2B7 rs7438135, UGT2B7 rs7439366, and UGT2B7 rs7662029 were associated with AcMPAG C0/D. Multiple linear regression analysis showed that UGT1A9 rs2741049 and indirect bilirubin were negatively correlated with MPAG C0/D (P=0.001; P=0.039). UGT2B7 rs7662029 was positively correlated with AcMPAG C0/D (P=0.008). In conclusion, the study shows a significant influence of UGT1A9 rs2741049 and UGT2B7 rs7662029 polymorphisms on the metabolism of MPA in vivo.