Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

01 December 2007

The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in caucasian liver transplant patients

A. Provenzani, M. Notarbartolo, F. Biondi, M. Labbozzetta, P. Poma, G. Vizzini, U. Palazzo, P. Polidori, F. Triolo, B. Gridelli, N. D'Alessandro

Ann Transplant 2008; 13(1): 33-33 :: ID: 880188


Background: Tacrolimus (TAC) is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCB1. We have investigated the effects of possible relevant CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) present in both donors and recipients on TAC blood levels achieved in a population of 32 Caucasian liver transplant patients.
Material/Methods: At 1, 3 and 6 months after transplantation, TAC doses (mg/kg/day) and trough blood levels were determined. Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*3 [6986A>G] as well as ABCB1 at exons 21 [2677G>T] and 26 [3435C>T].
Results: 87.5% of the population showed a CYP3A5*3/*3 genotype. For the ABCB1 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, TAC dose requirements were higher in patients receiving a liver with one copy of the *1 allele compared to those homozygous for the *3 allele (0.111±0.057 vs. 0.057±0.030 [P<0.05] at 3 month and 0.086±0.051 vs. 0.044±0.025 [P<0.05] at 6 month). For the recipients' genotypes, the presence of at least one *1 copy tended, though not statistically significantly, to increase TAC doses. With regard to the ABCB1 SNPs they did not show any influence on TAC dosing requirements.
Conclusions: Pharmacogenetic analysis of CYP3A5 in the donor could contribute to determine the appropriate initial dosage of tacrolimus in liver transplant patients.

Keywords: Tacrolimus, cytochrome, Liver Transplant


Most Viewed Current Articles

26 Jan 2022 : Review article  

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

DOI :10.12659/AOT.934924

Ann Transplant 2022; 27:e934924

24 Aug 2021 : Review article  

Normothermic Machine Perfusion (NMP) of the Liver – Current Status and Future Perspectives

DOI :10.12659/AOT.931664

Ann Transplant 2021; 26:e931664

29 Dec 2021 : Original article  

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...

DOI :10.12659/AOT.933588

Ann Transplant 2021; 26:e933588

15 Mar 2022 : Case report  

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...

DOI :10.12659/AOT.935860

Ann Transplant 2022; 27:e935860

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358