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

• Published in: Transplantation proceedings Vol. 56; no. 6; pp. 1280 - 1289
• Main Authors: Xu, Caomei, Jiang, Zhenwei, Qian, Minyan, Zuo, Li'an, Xue, Hui, Hu, Nan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2024
• Subjects: Adult; Female; Genotype; Glucuronides - blood; Glucuronosyltransferase - genetics; Humans; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid - pharmacokinetics; Polymorphism, Single Nucleotide; UDP-Glucuronosyltransferase 1A9
• ISSN: 0041-1345; 1873-2623; 1873-2623
• DOI: 10.1016/j.transproceed.2024.05.039

•Eleven UGT SNP loci were simultaneously assessed and a comprehensive analysis of their effects conducted, along with clinical factors, on mycophenolic acid metabolism.•Patients who carry the UGT1A9 rs2741049 TT genotype might be at a greater risk of a lower dose-adjusted MPAG C0.•UGT2B7 rs7662029 GG genotype carriers may face a higher risk of AcMPAG C0 after high-dose adjustment.
This study aimed to evaluate the effects of UDP-glucuronosyltransferase (UGT) polymorphisms on mycophenolic acid (MPA) metabolism in renal transplant patients. A total of 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 plasma concentration (C0/D) of 7-O-MPA-glucuronide (MPAG), and the dose-adjusted plasma concentration (C0/D) of acyl MPAG (AcMPAG) were analyzed. In the univariate analysis, UGT1A1 rs4148323, age, and anion gap were associated with MPA AUC/D. MPA AUC/D was higher in patients with the GA genotype of UGT1A1 rs4148323 compared to patients with the GG genotype. UGT1A1 rs4148323, UGT1A9 rs2741049 and clinical factors, including age, serum total bilirubin, adenosine deaminase, anion gap, urea, and creatinine, were associated with MPAG C0/D. UGT2B7 rs7438135, UGT2B7 rs7439366, and UGT2B7 rs7662029 also 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 = .001; P = .039), and UGT2B7 rs7662029 was positively correlated with AcMPAG C0/D (P = .008). This study demonstrates a significant influence of UGT1A9 rs2741049 and UGT2B7 rs7662029 polymorphisms on the metabolism of MPA in vivo.