title: Associations of UDP-glucuronosyltransferases polymorphisms with mycophenolate mofetil pharmacokinetics in Chinese renal transplant patients.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Xiao-chun
authors: XC
authors: Xie
authors: Kidney Transplant Department, Transplant Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Jun
authors: J
authors: Li
authors: Kidney Transplant Department, Transplant Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Hong-yang
authors: HY
authors: Wang
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Hong-liang
authors: HL
authors: Li
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Jing
authors: J
authors: Liu
authors: Kidney Transplant Department, Transplant Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Qian
authors: Q
authors: Fu
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Jia-wen
authors: JW
authors: Huang
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Chen
authors: C
authors: Zhu
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Guo-ping
authors: GP
authors: Zhong
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Xue-ding
authors: XD
authors: Wang
authors: Department of Pharmacy, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Ping-ping
authors: PP
authors: Sun
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Min
authors: M
authors: Huang
authors: Kidney Transplant Department, Transplant Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors: Chang-xi
authors: CX
authors: Wang
authors: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Jia-li
authors: JL
authors: Li
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D001711:Biotransformation; D016009:Chi-Square Distribution; D002681:China; D002851:Chromatography, High Pressure Liquid; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D020719:Glucuronides / Q000493:pharmacokinetics; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: D020719:Glucuronides; D007166:Immunosuppressive Agents; C000715591:UGT1A9 protein, human; C113145:mycophenolic acid glucuronide; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; C524630:UGT1A7 protein, human; D009173:Mycophenolic Acid