Başkent Üniversitesi Yayınları

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    Methylenetetrahydrofolate Reductase C677T Genotypes and Clinical Outcome Following Hematopoietic Cell Transplant
    (Başkent Üniversitesi, 2007-12) Azarpira, Negar; Geramizadeh, Bita; Darai, Masumeh; Aghdaie, Mahdokht Hossein; Ramzi, Mani
    Objective: Methotrexate may be used as a prophylactic agent against graft-versus-host disease in hematopoietic cell transplant. The drug exerts its effect on folate metabolism; 5,10-methylenetetra­hydrofolate reductase is a critical enzyme involved in this cycle and is related to the toxicity of methotrexate. Methods: We examined the association of a single nucleotide polymorphism at position 677 in the 5,10-methylenetetrahydrofolate reductase gene and the clinical outcomes of patients treated with allogeneic hematopoietic cell transplant. Genotyping of 5,10-methylenetetrahydrofolate reductase was performed by polymerase chain reaction-restriction fragment length polymorphism on 30 patients receiving hematopoietic cell transplant and their HLA-matched related donors. Patients were given a short course of methotrexate as prophylaxis to prevent graft-versus-host disease. Results: Donors and recipients who carried a 677T allele showed mildly higher total bilirubin, aspartic transaminase, and alanine transaminase levels, but these increases above the normal values were not statistically significant (P > .05). The platelet recovery to 20 000/µL and granulocyte recovery to 500/µL were slower for patients who carried a 677T allele, but these correlations also were not statistically significant. The 5,10-methylenetetrahy­dro­folate re­duct­ase genotypes of neither the donors nor the recipients had any effect on the incidence of acute graft-versus-host disease. Conclusions: No association was observed between the C677T polymorphism and the outcome parameters for any of the different genotypes studied here. Additional studies with larger samples are necessary to further elucidate the influence of 5,10-methylenetetrahydrofolate reductase genotyping on clinical outcomes of patients treated with hemato­poietic cell transplant who receive methotrexate.
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    Cytokine Gene Polymorphisms in Renal Transplant Recipients
    (Başkent Üniversitesi, 2006-12) Azarpira, N.; Aghdaie, MH.; Geramizadeh, B.; Behzadi, S.; Nikeghbalian, S.; Sagheb, F.; Rahsaz, M.; Behzad-Behbahanie, A.; Ayatollahi, M.; Darai, M.; Azarpira, MR.; Banihashemie, M.; Tabei, SZ.
    Objective: Acute rejection remains an important cause of graft loss after renal transplantation, and cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. However, the influence of gene polymorphisms on the functional immune response of transplant recipient outcomes remains controversial. Materials and Methods: The amplification refractory mutation system polymerase chain reaction was used to detect the interleukin-10 (IL-10) (-1082 G/A), tumor necrosis factor-alpha (TNF-α) (-308 G/A), and interferon-gamma (IFN-γ) (+874 T/A) single nucleotide polymorphisms in 100 of the first adult kidney recipients at our institution who were receiving cyclosporine-based immunosuppressive therapy. The diagnosis of acute rejection was based on clinical and histologic findings according to the Banff criteria. Results: The results of multivariate analyses showed no significant association between episodes of acute rejection and single nucleotide polymorphisms in IL-10, TNF-α genes, or dinucleotide repeat polymorphisms in the IFN-γ gene. Conclusions: Our results demonstrate that cytokine gene polymorphisms did not influence the early outcome of kidney transplantation.