Polymorphism was performed on Methylenetetrahydrofolate Reductase (MTHFR) 677 gene in which there is alanine-to-valine substitution. This polymorphism makes a reduction in MTHFR enzyme activity which results in increases in the methylene THF pool, which itself results in reduction in the mis-incorporation of uracil into DNA during DNA synthesis. These events cause double-strand breaks during uracil excision repair processes. Previous studies had shown that individuals with MTHFR 677 Homozygous mutation (677TT) have a reduced incidence of acute lymphoblastic leukemia (ALL), where a second common MTHFR polymorphism occurs at position 1298, which affects glutamate-to-alanine (A → C) change and accordingly a decrease in the enzyme activity. The present study aimed to evaluate the role of the two common polymorphisms in the MTHFR genes (C677T and A1298C) either individually or combined to determine the susceptibility risk to adult ALL in a population of Egyptian patients. DNA from 50 ALL cases and 100 controls were extracted from blood samples. Both polymorphic MTHFR C677T and A1298C Genotypes were screened by polymerase chain reaction and Restriction Fragment Length Polymorphism (PCR- RFLP). Results: The MTHFR 677 CT and TT mutation associated with a decreasing risk in ALL patients by 1.038 fold and 2.097 fold, respectively. The MTHFR 1298AC mutation and 1298CC associated with a decreasing risk in Egyptian ALL by 0.71 fold 1.474 fold, respectively. Combined homozygosity for both 677TT and 1298CC associated with a decrease in MTHFR activity, which affects the decreases in the susceptibility to adult ALL by 2.96 fold.
Key words: MTHFR, Polymorphism, Adults ALL.