Effects of Methylene Tetrahydro Folate Reductase Gene Polymorphisms on Methotrexate Toxicity in Egyptian Pediatric Acute Lymphocytic Leukaemia Patients

Document Type : Research article


1 Department of Pharmacology, Faculty of Medicine, Beni-Suef University, Egypt.

2 Deparment of Pharmacology, Faculty of Medicine, Jouf University, Saudia Arabia.

3 Department of Pediatric Oncology, National Cancer Institute, Cairo University, Egypt.

4 Department of Clinical Pathology, National Cancer Institute, Cairo University, Egypt.


This study was designed to evaluate the effect of Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms on MTX toxicity in pediatric Egyptian ALL patients. Ninety-Four of Pediatric ALL patients aged 3–13 years (7.6 ± 3.6) on oral maintenance dose of 50 mg/m2 weekly of MTX. MTHFR c.677C>T (rs1801133) and c.1298A>C (rs1801131) genotyping were performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The allele frequencies of c.677C>T were 42.6%, 46.8%, and 10.6% for CC, CT, and TT respectively, while c.1298A>C alleles frequencies were62.7%, 24.5%, and 12.8% for AA, AC, and CC respectively. None of the investigated polymorphism (C677T or A1298C alleles) was associated with either overall or site specific MTX toxicity regarding anemia (p = 0.99) (p = 0.4), platelets (p = 0.4) (p = 0.4), hepatotoxicity (p = 0.4) (p = 0.7), respectively. The results indicated that between c.677C>T genotypes, CC/CT and TT were associated with hematopoietic toxicities 60.7% and 60% (p = 0.2); platelet toxicities 76.2% and 80% (p = 1) and, hepatotoxicities 40.5% and 60% (p = 0.3), respectively. In the c.1298A>C genotypes, CC/AC and AA presented hematopoietic toxicities 68.6% and 55.9% (p = 0.2), platelet toxicities 82.9% 72.9% (p = 0.3) and, hepatotoxicity 37.1% and 45.8% (p = 0.5), respectively. No significant associations were detected between MTHFR c.677C>T or c.1298A>C polymorphisms and either overall or site specific MTX toxicity.