title: Genetic variance in ABCB1 and CYP3A5 does not contribute toward the development of chronic kidney disease after liver transplantation.
abstract: BACKGROUND
  Chronic kidney disease (CKD) after liver transplantation (LT) is a major clinical problem that appears to be associated with nongenetic as well as genetic determinants. Calcineurin inhibitor (CNI) use is considered to play a major role in the development of CKD after LT. We studied the influence of single-nucleotide polymorphisms (SNPs) in the genes of the donor and recipient CNI-metabolizing enzyme CYP3A5 and the CNI-transporting ABCB1 on the development of CKD after LT.
  
  
  METHODS
  Tacrolimus (Tac) predose concentrations at different time-points after transplantation and the CYP3A5 6986A>G and ABCB1 3435C>T SNPs were determined in 125 LT recipients and their respective donors to study the influence of Tac predose levels and genetics on the development of CKD.
  
  
  RESULTS
  After a median follow-up of 5.7±2.9 years, CKD developed in 47 patients (36%). The Tac predose levels were not correlated with the development of CKD. Neither did we find a correlation between the investigated SNPs in either donor or recipient ABCB1 and CYP3A5 genes (or combinations thereof) and the development of CKD. These genetic variations did not relate to Tac predose blood concentrations in our study.
  
  
  CONCLUSIONS
  An individual's risk of developing CKD after LT is not associated with genetic variation in either recipient or donor CYP3A5 or ABCB1 genotype status.
authors.affiliation: Departments of aGastroenterology and Hepatology bInternal Medicine cClinical Chemistry dSurgery eHospital Pharmacy, Clinical Pharmacology Unit; Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Tapirdamaz
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.forename: Samira
authors.initials: S
authors.lastname: el Bouazzaoui
authors.forename: Mohammad
authors.initials: M
authors.lastname: Azimpour
authors.forename: Bettina
authors.initials: B
authors.lastname: Hansen
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
authors.forename: Wojciech G
authors.initials: WG
authors.lastname: Polak
authors.forename: Jaap
authors.initials: J
authors.lastname: Kwekkeboom
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000328:Adult; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D054796:Drug Dosage Calculations; D005260:Female; D056726:Genetic Association Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000235:genetics; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D065095:Calcineurin Inhibitors; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus