Importance of MDR1 Gene Polymorphisms for Calcineurin Inhibitors Dosage and Early Kidney Graft Function, The
Clinic of Nephrology, Clinical Center of Serbia, Belgrade, Serbia
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia
School of Medicine, University of Belgrade, Belgrade, Serbia
Meeting: 2013 American Transplant Congress
Abstract number: B1136
Calcineurin inhibitors (CNIs) are a substrate of P-glycoprotein, the product of the multidrug resistance (MDR1) gene and has been known to undergo extensive hepatic metabolism by cytochrome P450 3A4 and CYP3A5.
The aim of this study was to examine the association of MDR1 gene polymorphism C3545T with dosage of CNIs and kidney graft function.
The study included 86 kidney transplant recipients, who have been treated by CNIs based immunosuppressive protocol. DNA was isolated from whole blood samples using a standard method. The purity of DNA was determined by measuring absorbance at 260 and 280 nm, respectively. Detection and analysis of MDR1 gene polymorphisms were performed using SSP-PCR method. During the first 6 months after transplantation CNI doses and levels, as well as frequency of acute rejection (AR) and delayed graft function (DGF), were recorded. We also followed the allograft function measured by serum creatinine concentration and creatinine clearance. AR was diagnosed by allograft biopsy, or on the basis of deterioration of allograft function which improved after high-dose of corticosteroid treatment. DGF is defined as a need for hemodialysis during the first 2 weeks after transplantation.
According to the results obtained for MDR1 gene polymorphism, patients were divided into two groups. Group one consisted of 21 patients with CC genotype, while the second group included 65 TC genotype patients. The groups did not differ regarding age and gender. There was no significant correlation between two genotypes and CNI doses during the first 6 months after Tx. However, allograft function measured by creatinine clearance was significantly better in the first group of patients the end of first (61.7 vs. 47.7 ml/min), third (63.0 vs. 55.06 ml/min) and sixth month after Tx (70.7 vs. 51.7 mL/min). Examined groups of patients did not differ with respect to frequency of DGF and AR.
In conclusion, our results suggest relationship between C3545T MDR1 gene polymorphism, and CNI dosage and allograft function, respectively. However, we have examined only one single nucleotide polymorphism in a relatively small number of patients, so further investigations on larger number of patients are necessary.
To cite this abstract in AMA style:
Kravljaca M, Pravica V, Savic E, Brkovic V, Lezaic V, Naumovic R. Importance of MDR1 Gene Polymorphisms for Calcineurin Inhibitors Dosage and Early Kidney Graft Function, The [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/importance-of-mdr1-gene-polymorphisms-for-calcineurin-inhibitors-dosage-and-early-kidney-graft-function-the/. Accessed May 14, 2025.« Back to 2013 American Transplant Congress