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Acta Medica Medianae
Vol. 52, No 1, March, 2013

UDK 61
ISSN 0365-4478(Printed version)
ISSN 1821-2794(Online)


Correspondence to:

 Nikola Stefanović

Faculty of Medicine

Department of Pharmacology

Bulevar dr. Zorana Đinđića br. 81 18000 Niš, Serbia

E-mail: snikola84@gmail.com

Original article                                                                    

UDC: 577.2:616.61-089.83






Nikola Stefanović, Tatjana Cvetković, Radmila Veličković-Radovanović,

Tatjana Jevtović-Stoimenov, Dijana Stojanović and Nataša Živković

University of Niš, Faculty of Medicine, Niš , Serbia


 Tacrolimus (FK-506) is a part of most immunosuppressive protocols after kidney transplantation because it significantly affects the survival of transplanted organs in post - transplantation period. FK-506 is characterized by a narrow therapeutic index and large interindividual variability in pharmacokinetics. Partly, these variations can be explained by 6986A>G polymorphism CYP3A5 gene. As a substrate for CYP3A5 isoenzyme, FK–506 has a different elimination rate amnog  individuals, which is caused by CYP3A5 gene polymorphism.

            The primary objective of this study was to investigate the frequency of CYP3A5 gene polymorphism (6986A>G) in kidney transplant patients and comparison with the healthy volunteers. The second objective of this study was to determine the influence of the investigated polymorphism on FK–506 dosage regimen one month after kidney transplantation.

Pharmacogenetic retrospective study included 121 examinees - 60 patients with renal transplant and 60 healthy volunteers. Patients have routine determination of drug concentration at the Clinic of Nephrology, Clinical Center Niš, Serbia. PCR method (Ashavaid TF et al.)  was used to determine the polymorphism of CYP3A5 gene.

            Our study did not show statistically significant differences in allele (p=0.616) and genotype (p=0.602) frequencies between the studied polymorphism in renal transplant patients and healthy volunteers. A statistically significant difference was found between patients with different genotypes of CYP3A5 regarding dose (p=0.001), weight adjusted dose (p=0.005), and dose normalized level of FK–506 (p=0.039) one month after transplantation.

             Patients with kidney transplant and healthy subjects in Serbian population did not show difference in the frequency of alleles of CYP3A5 gene. CYP3A5 gene polymorphism affects the dose regimen of tacrolimus one month after kidney transplantation. Acta Medica Medianae 2013;52(1):33-38.


      Key words: tacrolimus, CYP3A5 polymorphism, pharmacogenetics, kidney transplant