Browsing by Author "Malekhoseini, Seid Ali"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Association Between Tacrolimus Concentration and Genetic Polymorphisms of CYP3A5 and ABCB1 During the Early Stage After Liver Transplant in an Iranian Population
    (Başkent Üniversitesi, 2012-02) Rahsaz, Marjan; Aghdaie, Mahdokht H.; Banihashemi, Mehrzad; Malekhoseini, Seid Ali; Malekpour, Zahra; Darai, Masumeh; Moini, Maryam; Geramizadeh, Bita; Nikeghbalian, Saman; Azarpira, Negar
    Objectives: Tacrolimus is widely used as an immunosuppressive drug in liver transplant recipients with a narrow therapeutic range and variable individualized pharmacokinetics. Tacrolimus is a substrate of cytochrome P-450 3A enzyme and the drug transporter, P-glycoprotein. Materials and Methods: We determined the genotypic frequencies of cytochrome P-4503A5 (rs776746), and ABCB1 (rs1045642), single nucleotide polymorphisms in a population of 100 Iranian liver transplant patients, and investigated the influence of the above-mentioned single nucleotide polymorphisms on tacrolimus concentrations. At 7 and 30 days after transplant, tacrolimus dosages (mg/kg/d), trough blood levels (T0), and dose-adjusted concentrations (concentration/dosage ratio) were determined. Polymerase chain reaction, followed by restriction fragment length polymorphism analysis, was used for genotyping cytochrome P-4503A5*3 [6986A>G] as well as ABCB1 [3435C>T]. Results: Ninety-five percent of the population showed a cytochrome P-4503A5*3/*3 genotype. ABCB13435TT genotype was observed in 33 cases (33%); whereas 51 cases (51%) carried 3435CT, and 16 cases (16%) carried 3435CC. With regard to the ABCB1 and cytochrome P-4503A5, they showed no influence on tacrolimus dosing requirements at 1 week or 1 month after transplant. No association of any genetic variant with the acute rejection rate was found. Conclusions: Finally, as the liver donor genotype influences tacrolimus pharmacokinetics with regard to expression of cytochrome P-4503A5, far more than the genotype of the recipient; therefore, it should be considered before recommending any personal immunosuppressive treatment based on pharmacogenetics.
  • No Thumbnail Available
    Item
    Thiopurine S-Methyltransferase Polymorphism in Iranian Kidney Transplant Recipients
    (Başkent Üniversitesi, 2011-08) Aghdaie, Mahdokht Hossein; Malekhoseini, Seid Ali; Rahsaz, Marjan; Darai, Masumeh; Sagheb, Mehdi; Geramizadeh, Bita; Azarpira, Negar
    Objectives: Thiopurine S-methyltransferase is an enzyme that catalyzes S-methylation of azathioprine as an immunosuppressive drug. Genetic polymorphisms influence thiopurine S-methyltransferase activity. There are 3 variant alleles: thiopurine S-methyltransferase*2, *3A, and *3C are responsible for more than 95% cases of low-enzyme activity. Materials and Methods: We studied these polymorphisms and the occurrence of azathioprine adverse effects in 50 renal transplant recipients undergoing triple immunosuppressive therapy including azathioprine, cyclosporine, and prednisone. Thiopurine S-methyltransferase genetic polymorphism was determined by polymerase chain reaction restriction fragment length polymorphism assay and allele-specific polymerase chain reaction methods. Azathioprine dosage; leukocyte, erythrocyte, and platelet counts; and graft rejection episodes were analyzed during hospitalization. Results: Two patients (2%) were heterozygous for thiopurine S-methyltransferase*3C, the remaining patients were thiopurine S-methyltransferase wild-type *1/*1 (98%). Thiopurine S-methyltransferase wild-type homozygous and heterozygous patients were administered similar azathioprine dosages at the beginning of treatment (2.42 ± 0.50 and 2.52 ± 0.40 mg/kg/24 h). During subsequent days, mean azathioprine dosage administered to thiopurine S-methyltransferase wild-type homozygous patients was similar to heterozygous patients, but with no statistical difference (P = .28). Three patients had an acute rejection episode during this time. Five patients (10%) had reduced azathioprine dosage owing to adverse effects. Adverse reactions consisted of hematotoxicity (n=2), hepatotoxicity (n=1), and gastrointestinal toxicity (n=2). All recipients were wild-type homozygotes. Conclusions: The frequency of thiopurine S-methyltransferase gene mutations is low among our patients. The incidence of adverse reactions to azathioprine was also low, even in patients carrying a variant of thiopurine S-methyltransferase. We conclude that determining thiopurine S-methyltransferase genotype is not useful in our population to predict adverse reactions to azathioprine.