The effect of CYP3A5 and ABCBl single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients

Alessio Provenzani, Monica Notarbartolo, Manuela Labbozzetta, Paola Poma, Filippo Biondi, Rosario Sanguedolce, Giovanni Vizzini, Ugo Palazzo, Piera Polidori, Fabio Triolo, Bruno Gridelli, Natale D'Alessandro

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCBl. We have investigated the effects of possible relevant CYP3A5 and ABCBl single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients. Material/Methods: At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were determined. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for gen-otyping CYP3A5*3 [6986A>G] as well as ABCBl at exons 21 [2677G>T] and 26 [3435C>T]. Results:87.5% of the population showed a CYP3A5*3/*3 genotype. For the ABCBl SNPs, in the case of 3435C>T the total frequency observed for the allelic variant was 50%. For the 2677G>T, the total frequency of the allelic variant was 12.5%, lower than in other Caucasian populations and without any significant linkage with 3435C>T. At 3 and 6 months after transplantation, tacrolimus dose requirements were significantly higher in patients receiving a liver with one copy of the *1 al-lele compared to those homozygous for the *3 allele (0.111±0.057 vs. 0.057±0.030 [P

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalAnnals of Transplantation
Volume14
Issue number1
Publication statusPublished - 2009

Keywords

  • ABCB1
  • CYP3A5
  • Liver transplant
  • Single nucleotide polymorphisms
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation
  • Medicine(all)

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