title: Donor ABCB1 genetic polymorphisms influence epithelial-to-mesenchyme transition in tacrolimus-treated kidney recipients.
abstract: OBJECTIVE
  The contribution of epithelial-mesenchymal transition (EMT) has been suggested in renal transplant recipients receiving calcineurin inhibitors and developing nephrotoxicity.
  
  
  METHODS
  We assessed whether interindividual variability in tacrolimus pharmacokinetics is associated with the occurrence in tubular cells of two EMT markers (vimentin, β-catenin) detected at 3-month in 140 allograft biopsies. We investigated whether genetic polymorphisms affecting CYP3A5 and ABCB1 influence EMT and kidney fibrosis.
  
  
  RESULTS
  In univariate analysis, the donor CYP3A5*1 allele was significantly associated with a lower vimentin expression. In multivariate analysis, grafts carrying ABCB1 3435T allele(s) developed significantly less EMT and less interstitial fibrosis.
  
  
  CONCLUSIONS
  Donor SNPs significantly influence the epithelial program in the context of kidney transplantation, and the epithelial metabolism of tacrolimus is one key to understand graft fibrogenesis.
authors.affiliation: EA4483, Faculté de Médecine H Warembourg, Pôle Recherche, Université de Lille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bloch
authors.forename: Marc
authors.initials: M
authors.lastname: Hazzan
authors.forename: Cynthia
authors.initials: C
authors.lastname: Van der Hauwaert
authors.forename: David
authors.initials: D
authors.lastname: Buob
authors.forename: Grégoire
authors.initials: G
authors.lastname: Savary
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hertig
authors.forename: Viviane
authors.initials: V
authors.lastname: Gnemmi
authors.forename: Marie
authors.initials: M
authors.lastname: Frimat
authors.forename: Michaël
authors.initials: M
authors.lastname: Perrais
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.forename: Franck
authors.initials: F
authors.lastname: Broly
authors.forename: Christian
authors.initials: C
authors.lastname: Noël
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pottier
authors.forename: Christelle
authors.initials: C
authors.lastname: Cauffiez
authors.forename: François
authors.initials: F
authors.lastname: Glowacki
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014019:Tissue Donors; D014746:Vimentin / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D014746:Vimentin; D051176:beta Catenin; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: ABCB1; CYP3A5; epithelial–mesenchymal transition; fibrosis; tacrolimus