Genetic Polymorphisms of MRP2 and UGT2B7 and Gastrointestinal Symptoms in Renal Transplant Recipients Taking Mycophenolic Acid

  title={Genetic Polymorphisms of MRP2 and UGT2B7 and Gastrointestinal Symptoms in Renal Transplant Recipients Taking Mycophenolic Acid},
  author={Jae Wook Yang and Puay Hoon Lee and Ian V. Hutchinson and Vera Pravica and Tariq Shah and David I. Min},
  journal={Therapeutic Drug Monitoring},
The aim of this study was to determine the relationship between single nucleotide polymorphisms in multidrug resistance protein 2 (MRP2) and uridine diphosphate glucuronosyltransferase (UGT) 2B7 and the severity of gastrointestinal (GI) symptoms in patients receiving mycophenolic acid (MPA). A total of 67 renal transplant recipients taking MPA derivatives were included in the study. Genotypes for MRP2 C-24 T and UGT2B7 C802 T were determined. The incidence and severity of GI symptoms were… 
Mycophenolic acid AUC in Thai kidney transplant recipients receiving low dose mycophenolate and its association with UGT2B7 polymorphisms
Most of patients with reduced mycophenolate dose had the AUC within the therapeutic range, and genetic polymorphisms in UGT2B7 may play a role in MPA metabolism in Thai kidney transplant patients.
The influence of UGT polymorphisms as biomarkers in solid organ transplantation.
Influence of SLCO1B1 521T>C, UGT2B7 802C>T and IMPDH1 −106G>A Genetic Polymorphisms on Mycophenolic Acid Levels and Adverse Reactions in Chinese Autoimmune Disease Patients
This study investigates the relationships between UGT1A9 −118(dT)9/10, UGT2B7 802C>T, SLCO1B1 521T>C, IMPDH1 −106G>A and MPA trough concentration, along with adverse reactions among Chinese patients with autoimmune diseases, to explore the genetic factors affecting MPA levels and adverse reactions.
Multi-institutional Study of Outcomes After Pediatric Heart Transplantation: Candidate Gene Polymorphism Analysis of ABCC2.
  • G. Burckart, W. Figg, S. Webber
  • Medicine, Biology
    The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG
  • 2014
As a candidate gene assessment, the ABCC2 rs717620 AG and AA genotypes may be associated with improved, rather than poorer, RHC in PHTx patients receiving MPA therapy.
Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer
Breast cancer patients carrying the UGT2B7268Tyr/Tyr genotype may benefit most from adjuvant epirubicin-based chemotherapy, and these results warrant confirmation in further studies.
ATP-binding cassette transporters as pharmacogenetic biomarkers for kidney transplantation.
Diabetes Mellitus Reduces Activity of Human UDP-Glucuronosyltransferase 2B7 in Liver and Kidney Leading to Decreased Formation of Mycophenolic Acid Acyl-Glucuronide Metabolite
It is suggested that diabetes mellitus is associated with significantly reduced UGT2B7 mRNA expression, protein level, and enzymatic activity of human liver and kidney, explaining in part the relatively low circulating concentrations of AcMPAG in diabetic patients.
Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update
Mycophenolate is now the antimetabolite of choice in immunosuppressant regimens in transplant recipients, and the role of therapeutic drug monitoring (TDM) is still controversial and the ability of routine MPA TDM to improve long-term graft survival and patient outcomes is largely unknown.


C-440T/T-331C polymorphisms in the UGT1A9 gene affect the pharmacokinetics of mycophenolic acid in kidney transplantation.
The study demonstrated a significant impact of C-440T/T-331C SNPs in the promoter region of the UGT1A9 gene on MPA pharmacokinetics in renal allograft recipients and confirmed large interpatient variability of MPA exposure.
Multidrug Resistance Protein 2 Genetic Polymorphisms Influence Mycophenolic Acid Exposure in Renal Allograft Recipients
The MRP2 C-24T and C-3972T polymorphisms protect renal transplant recipients from a decrease in MPA exposure associated with mild liver dysfunction and are suggested to be associated with a lower oral clearance of MPA in steady-state conditions.
Irinotecan‐induced Diarrhea: Functional Significance of the Polymorphic ABCC2 Transporter Protein
This study suggests that the presence of the ABCC2*2 haplotype is associated with less irinotecan‐related diarrhea, maybe as a consequence of reduced hepatobiliary secretion of irinOTecan.
Influence of the UGT2B7 promoter region and exon 2 polymorphisms and comedications on Acyl-MPAG production in vitro and in adult renal transplant patients
In vitro and in vivo, AcMPAG production was increased in corticosteroid-induced rat liver microsomes, consistent with the observed in-vivo decrease of mycophenolic acid metabolites AUC0–9 h/dose with time after transplant.
Influence of Nonsynonymous Polymorphisms of UGT1A8 and UGT2B7 Metabolizing Enzymes on the Formation of Phenolic and Acyl Glucuronides of Mycophenolic Acid
Several UGT1A8 variants identified may potentially account for the large interindividual variance in MMF pharmacokinetics and deserve further clinical investigations.
The Impact of UGT1A8, UGT1A9, and UGT2B7 Genetic Polymorphisms on the Pharmacokinetic Profile of Mycophenolic Acid After a Single Oral Dose in Healthy Volunteers
After a single oral dose of MMF in healthy volunteers, specific UGT genotypes significantly alter MPA PKs and this clearly warrants additional studies with complete and detailed genetic profiling of UGT 1A8, UGT1A9, and UGT2B7 genes.
Enteric‐Coated Mycophenolate Sodium can be Safely Administered in Maintenance Renal Transplant Patients: Results of a 1‐Year Study
  • K. Budde, J. Curtis, M. Hall
  • Medicine
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2004
In conclusion, renal maintenance patients can be converted from MMF to EC‐MPS without compromising the safety and efficacy profile associated with MMF.
Using GI-specific patient outcome measures in renal transplant patients: Validation of the GSRS and GIQLI
The GSRS and the GIQLI are appropriate for use in a post-renal transplant population and demonstrated significant differences between renal transplant patients with GI complications and without GI complications.
Patient-Reported Gastrointestinal Symptom Burden and Health-Related Quality of Life following Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium
This first exploratory study indicates that converting patients with mild, moderate or severe GI complaints from MMF to EC-MPS significantly reduces GI-related symptom burden and improves patient functioning and well-being.
Mycophenolate Mofetil Dose Reductions and Discontinuations after Gastrointestinal Complications Are Associated with Renal Transplant Graft Failure
Renal transplant recipients who underwent Mycophenolate mofetil dose reduction or withdrawal following GI diagnosis are associated with increased risk of graft failure.