Background and Aim: Acute lymphoblastic leukemia patients show differences in serum levels and toxicity associated with methotrexate after its treatment. Pharmacogenetics is an important determining factor for these differences. In this study, the effect of +452 C / T and -401C / T polymorphisms of GGH gene on serum levels and toxicity associated with methotrexate was studied. The aim of this study was to evaluate the effect of +452C / T and -401C / T polymorphisms of GGH gene on methotrexate level in serum and its associated toxicity in patients with acute lymphoblastic leukemia. Furthermore, the frequency of the above polymorphisms was investigated for the first time in Iran. Materials and Methods: The prevalence of these polymorphisms was assessed in 83 Iranian patients with ALL using PCR and RFLP. The relationship between the polymorphism and serum methotrexate levels and its toxicity was estimated by calculating the Odds Ratio. Results: No correlation was found between +452CT polymorphism and serum levels of methotrexate and methotrexate-related toxicity. -401CT polymorphism was found to be correlated with methotrexate-related toxicity leading to thrombocytopenia (95% CI= 0.009-0.019, odds ratio=0.265) and leukopenia (95% CI = 0.021-0.042, odds ratio = 2.182) in consolidation phase of the treatment. Conclusion: Evaluation of patients for methotrexate-related polymorphism of GGH gene may be useful in selecting the appropriate dose of methotrexate and reducing the toxic side effects associated with its administration.
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