title: Liver Transplant Patient Carriers of Polymorphism Cyp3a5*1 Donors May Need More Doses of Tacrolimus From the First Month After Transplantation.
abstract: BACKGROUND
  The aim of this work was to evaluate the CYP3A5:CYP3A5*1/CYP3A5*3 (6986A>G) polymorphism related to the pharmacokinetic characteristics of tacrolimus during the first 3 months after transplantation, analyzing both donor and recipient genotype, in liver transplant patients.
  
  
  METHODS
  This retrospective, single-center, cohort study included patients who had been treated with tacrolimus monotherapy with or without corticoids (n = 67). Donors and recipients were genotyped for the CYP3A5*3 allele polymorphism (6986A>G) by use of a TaqMan polymerase chain reaction technique. The presence or absence of the *1 allele ("minor-allele") was analyzed for correlation with the tacrolimus dose-normalized ratio during the 3 months after transplantation.
  
  
  RESULTS
  The following observations were obtained in the population studied: (1) Frequency of the minor allele*1 was much lower both in recipients (11.9% versus 88.1%) and donors (19.4% versus 80.6%), with no statistically significant differences between both distributions. (2) Recipient genotype for CYP3A5*1/*3-polymorphism had no influence in tacrolimus pharmacokinetics, with no differences between carriers and non-carriers of the minor-allele*1. (3) However, from the first month after transplantation, patients with grafts from donor carriers of minor allele*1 had lower concentration-dose ratios compared with patients with grafts from donor non-carriers of that allele (71.1 versus 119.3 and 90.5 versus 126.3, for 30 and 90 days after transplantation, respectively; P < .05).
  
  
  CONCLUSIONS
  The presence of the CYP3A5-6986A>G-polymorphism in the donor affects tacrolimus pharmacokinetics in the recipient, although the difference was statistically significant only for the first month after transplantation. This means that in liver transplant patients receiving grafts from donors carrying the CYP3A5*1-polymorphism, a larger dose of tacrolimus from the first month after transplantation would be needed. The evidence provided in this study showed no effect of the recipient genotype.
authors.affiliation: Toxicology, Labco Diagnostics, Esplugues de Llobregat, Barcelona, Spain. Electronic address: anargudo@hotmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Argudo
authors.affiliation: Laboratori Clínic, Bellvitge-IDIBELL University Hospital, University of Barcelona, L'Hospitalet, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: González de Aledo
authors.affiliation: Laboratori Clínic, Bellvitge-IDIBELL University Hospital, University of Barcelona, L'Hospitalet, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Alía
authors.affiliation: Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Ramírez
authors.affiliation: Pathology Department, Bellvitge-IDIBELL University Hospital, University of Barcelona, L'Hospitalet, Barcelona, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Serrano
authors.affiliation: Liver Transplant Unit, Bellvitge-IDIBELL University Hospital, University of Barcelona, L'Hospitalet, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Fabregat
authors.affiliation: Liver Transplant Unit, Bellvitge-IDIBELL University Hospital, University of Barcelona, L'Hospitalet, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Castellote
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008099:Liver; D008103:Liver Cirrhosis / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D014019:Tissue Donors; D019737:Transplants
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D011241:Prednisone; D016559:Tacrolimus