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The Effect of Polymorphisms of Gamma-Glutamyl Hydrolase (Ggh) Gene on Methotrexate-Induced Toxicity in Acute Lymphoblastic Leukemia Publisher



Kalantari A1 ; Zaker F2 ; Ansari S3 ; Sharafi H4 ; Mohammadian M5, 6
Authors
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Authors Affiliations
  1. 1. Department of Hematology, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Haematology, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pediatric Hematology-Oncology, Ali Asghar Childrens Hospital, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Baqiyatallah Research Center for Gastroentrology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran
  5. 5. Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran
  6. 6. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Toxin Reviews Published:2015


Abstract

Context: Acute lymphoblastic leukemia patients show differences in methotrexate-induced toxicity after treatment with this anti-cancer drug. Pharmacogenetics is an important determining factor for toxicity diversity. Objective: In this study, the effect of +452 CT and 401CT polymorphisms of Gamma-glutamyl hydrolase (GGH) gene on methotrexate serum levels and its associated toxicity in patients with acute lymphoblastic leukemia was assessed. Furthermore, the frequency of the above polymorphisms was investigated for the first time in Iran. Material 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. Discussion: C allele polymorphism of-401 C/T allele is a risk factor of leukopenia and thrombocytopenia in patients treated with methotrexate. Moreover, our results suggested that the T allele had a supporting role in prevention of thrombocytopenia. Conclusion: Evaluation of patients for methotrexate-related polymorphism of GGH gene may be useful to determine the appropriate dose of methotrexate and reducing its toxic side effects. © 2015 Taylor & Francis.