title: The importance of MDR1 gene polymorphisms for tacrolimus dosage.
abstract: Polymorphisms of the multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and their haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method. Patients with variant alleles for SNPs G2677T/A and C3435T required higher doses of tacrolimus and had a lower level/dose (L/D) ratio than patients with wild alleles or heterozygotes. That difference was the most obvious for SNP G2677T/A where TT homozygotes required significantly higher doses of tacrolimus during whole follow-up. Their L/D was significantly lower in the first month after transplantation. Recipients with CTT/TTT haplotype also had lower L/D than those with CGC/TTT and CGC/CGC, significantly in the 10th and 20th days after transplantation respectively (p<0.05). Our results demonstrate that TT homozygotes at positions G2677T/A and C3435T required a higher tacrolimus dose than those with wild alleles or heterozygotes. It may be helpful in the prevention of tacrolimus nephrotoxicity early after transplantation.
authors.affiliation: Clinic of Nephrology, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia. Electronic address: mkravljaca@gmail.com.
authors.forename: Milica
authors.initials: M
authors.lastname: Kravljaca
authors.affiliation: Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Perovic
authors.affiliation: Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Pravica
authors.affiliation: Clinic of Nephrology, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia.
authors.forename: Voin
authors.initials: V
authors.lastname: Brkovic
authors.affiliation: Clinic of Nephrology, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Milinkovic
authors.affiliation: Clinic of Nephrology, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Lausevic
authors.affiliation: Clinic of Nephrology, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia; School of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
authors.forename: Radomir
authors.initials: R
authors.lastname: Naumovic
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
keywords: Kidney transplantation; MDR1 gene polymorphisms; Pharmacokinetics; Tacrolimus