Başkent Üniversitesi Yayınları

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Author: search.filters.author.Azarpira, NegarSubject: search.filters.subject.Transplant

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    Vitamin D Receptor Genotype in Pancreas Allograft: A Pilot Study
    (Başkent Üniversitesi, 2012-10) Rahsaz, Marjan; Esfandiari, Elaheh; Aghdaie, Mahdokht Hossein; Daraie, Masumeh; Karimi, Mohammad Hossein; Yaghubi, Ramin; Ayatollahi, Maryam; Geramizadeh, Bita; Nikeghbalian, Saman; Azarpira, Negar
    Objectives: Transplanting of pancreatic grafts is an established treatment for diabetes mellitus. Polymorphisms in genes, coding for proteins involved in an immune response, may influence immunologic and nonimmunologic mechanisms that lead to allograft loss. Vitamin D receptor agonists have been shown to increase long-term allograft survival in humans. Materials and Methods: Twenty-one pancreatic recipients transplanted in the Transplantation center of Shiraz University of Medical Sciences were selected and genotyped for the polymorphism of the vitamin D receptor genes (FokI), and the association of each genotype with acute rejection was evaluated. A control group of 100 unrelated otherwise healthy individuals, from the Iranian Blood Transfusion Organization were enrolled. The individuals were selected from Shiraz (a city located in Southern Iran), and the genotype frequency was compared with control group. Results: The overall prevalence acute rejection was 28% (6/21). In the genotype study, homozygous FF presented in 15 patients (71%), heterozygous Ff presented in 6 patients (29%), and no homozygous ff was identified. In the control group, there were 50% with FF, 48% with Ff, and 2% with the ff genotype identified. The only genotype that was detected in rejection group was FF, while the frequency of FF in the nonrejection group was 60%. Conclusions: This study examined several patients to determine whether the vitamin D receptor (FokI) genotype is involved in acute allograft rejection and requires deeper investigation.
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    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.