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

This study was designed to evaluate the effect of Methylenetetrahydrofolate reductase ( 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/m 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 were 42.6%, 46.8%, and 10.6% for , and respectively while c.1298A>C alleles frequencies were 62.7%, 24.5%, and 12.8% for , and respectively. None of the investigated polymorphism ( or alleles) was associated with either overall or site specific MTX toxicity regarding anemia ( 0.99) ( 0.4), platelets ( 0.4) ( 0.4), hepatotoxicity ( 0.4) ( 0.7), respectively. The results indicated that between genotypes, and were associated with hematopoietic toxicities 60.7% and 60% ( 0.2); platelet toxicities 76.2% and 80% ( 1) and, hepatotoxicities 40.5% and 60% ( 0.3), respectiv. In the genotypes, and AA presented hematopoietic toxicities 68.6% and 55.9% ( 0.2), platelet toxicities 82.9% 72.9% ( 0.3) and, hepatotoxicity 37.1% and 45.8% ( 0.5), respectively. No significant associations were detected between or polymorphisms and either overall or site specific MTX toxicity.