Türkiye organ nakli kuruluşları koordinasyonu derneği IX kongresi, Transplantasyon 12, Bursa, Turkey, 1 - 04 September 2012, pp.20
Background: Tacrolimus, is a member of the calcineurin inhibitör family. It is used to prevent allograft rejection in renal transplantation. Tacrolimus has narrow therapeutic index. Moreover, the blood concentration of and tacrolimus after standard dose application of the drugs to patients with renal transplant showed significant difference between individuals. It is showed with various research that absorption and metabolism of this drug is changed by multidrug resistance (MDR)1 gene polymorphisms. Some of the single nucleotide polymorphisms (SNP) of MDR1 reported correlated with the in vivo activity of P-gp. The aim of this study was to investigate the association of the MDR1 gene (C3435T) polymorphism with tacrolimus blood concentration and dose requirements, acute rejection episodes in Turkish renal transplant patients.
Material and methods: 100 patients had transplants from living donors and 150 healthy controls were included to this study. C3435T genotyping for patient and control groups were performed using polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP). Blood concentrations of tacrolimus were determined with Cloned Enzyme Donor Immunoassay (CEDIA).
Results: The genotype frequencies CC, CT and TT were 44.0%, 33.0% and 23.0% for patients respectively. The genotype frequencies CC, CT and TT were 36.7%, 43.3% and 20.0% for controls respectively. There was no different between patients and controls (p= 0.061, p=102, p=0,211 respectively). The ratio of blood concentration/dose of tacrolimus for patients with mutant homozygous 3435 TT genotype was found higher than of patients with wild -type homozygous for the 3435 CC genotype, and the dose given to these patients were observed to be lower at 1. 3. and 12. months respectively (p=0.048, p=0.03, p=0.041). There were no statistically significant difference between groups regarding to usage of drugs which may affect on tacrolimus blood concentration like diltiazem. No association of any genetic variant with the acute rejection rate was found. Acute rejection was not associated with the CC genotype vs CT and TT genotypes: OR=0.517; 95%CI (0.190–1.407); p=0.192, OR=1.558; 95%CI (0.587–4.136); p=0.372, OR=1.346; 95%CI (0.456–3.968); p=0.590 respectively.
Conclusion: MDR1 polymorphism can be useful to adjust the optimal dose os tacrolimus in reanl transplant patients and may be help to achieving target of tacrolimus blood concentarions. Also MDR1 polymorphism could be help to reducing acute rejection episodes.