title: ABCB1 (MDR-1) pharmacogenetics of tacrolimus in renal transplanted patients: a Next Generation Sequencing approach.
abstract: BACKGROUND
  A CYP3A5 gene polymorphism is the main determinant of Tacrolimus (Tac) dose requirements among renal transplanted patients. In spite of the utility of CYP3A5 genotyping to predict the Tac-dose, many patients exhibit an out of range blood Tac level and it is thus likely that other genes/polymorphisms contribute to define Tac bioavailability. To address this issue we searched for coding sequence variants in the ABCB1/MDR1 gene in renal transplanted patients treated with Tac and who had out of the range blood levels.
  
  
  METHODS
  We studied 100 renal transplanted patients treated with Tac, 60 of whom had Tac blood levels below (n=39) and above (n=21) the target range (10-15 ng/mL) at 1 week post-transplant. The DNA was subjected to multiplex amplification followed by massive parallel semiconductor sequencing in the Ion Torrent personal genome machine.
  
  
  RESULTS
  We found four missense changes, all reported and present in cases above and below the blood Tac target. In addition, we did not find differences in the allele and genotype frequencies for the common rs1045642 polymorphism (p.I1145I) between the groups.
  
  
  CONCLUSIONS
  Our results suggested that the ABCB1 variants had no effect on the risk of showing out of range Tac blood levels among renal transplanted patients.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tavira
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.forename: Carmen
authors.initials: C
authors.lastname: Diaz-Corte
authors.forename: Beatriz
authors.initials: B
authors.lastname: Suarez
authors.forename: Diego
authors.initials: D
authors.lastname: Coronel
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.forename: Sara
authors.initials: S
authors.lastname: Iglesias
authors.forename: Belén
authors.initials: B
authors.lastname: Alonso
authors.forename: Emilio
authors.initials: E
authors.lastname: Rodrigo
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000483:Alleles; D054316:Biomarkers, Pharmacological / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000379:methods*; D020125:Mutation, Missense; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D054316:Biomarkers, Pharmacological; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus