title: SLCO1B1 genetic polymorphism influences mycophenolic acid tolerance in renal transplant recipients.
abstract: OBJECTIVE
  This study aimed to determine the influence of gene candidates on mycophenolic acid (MPA) response during the first year of renal transplantation.
  
  
  METHODS
  A total of 218 renal transplant recipients who received MPA from the first day of transplantation at a fixed dose of 2 g/day were genotyped for ABCB1, ABCC2, UGT2B7, UGT1A9, SLCO1B1, SLCO1B3 and IMPDH1 polymorphisms. Clinical end points were MPA-related adverse drug reactions (ADRs) and acute rejection episodes during the first year post-transplantation.
  
  
  RESULTS
  After correction for multiple statistical testing, SLCO1B1 (encoding the hepatic uptake transporter OATP1B1) was the only gene associated with MPA-related ADRs, showing a 75% risk reduction in favor of a protective effect of the SLCO1B1*5 allele (p = 0.002). In vitro experiments showed that MPA metabolites MPA-phenyl-glucuronide and MPA-acyl-glucuronide are substrates of OATP1B1. Their transport was decreased in the presence of the variant transporter (OATP1B1*5).
  
  
  CONCLUSIONS
  These results suggest for the first time that carriers of the SLCO1B1*5 allele seem to be protected from MPA-related ADRs.
authors.affiliation: Pharmacology Department, Univ Paris-Sud, Bicêtre University Hospital, le Kremlin, Bicêtre, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Michelon
authors.forename: Jörg
authors.initials: J
authors.lastname: König
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Lina
authors.initials: L
authors.lastname: Quteineh
authors.forename: Céline
authors.initials: C
authors.lastname: Verstuyft
authors.forename: Valérie
authors.initials: V
authors.lastname: Furlan
authors.forename: Sophie
authors.initials: S
authors.lastname: Ferlicot
authors.forename: Alexia
authors.initials: A
authors.lastname: Letierce
authors.forename: Bernard
authors.initials: B
authors.lastname: Charpentier
authors.forename: Martin F
authors.initials: MF
authors.lastname: Fromm
authors.forename: Laurent
authors.initials: L
authors.lastname: Becquemont
mesh_terms: D001711:Biotransformation / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000235:genetics* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation; D007962:Leukocytes / Q000378:metabolism; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D027361:Organic Anion Transporters / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013379:Substrate Specificity; D014162:Transfection
chemical_list: C000715087:ABCC2 protein, human; D007166:Immunosuppressive Agents; D027381:Liver-Specific Organic Anion Transporter 1; D000089762:Multidrug Resistance-Associated Protein 2; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D004247:DNA; D009173:Mycophenolic Acid