C677T and A1298C polymorphisms of Methylenetetrahydrofolate reductase (MTHFR) gene: Effect and risk to develop chronic myeloid leukemia: A study on Syrian patients

Methylenetetrahydrofolate reductase (MTHFR) gene is essential in folate metabolism. Genetic variations in this gene like 677 C>T and 1298 A>C affect its activity; the latter could act efficiently the DNA methylation and may give susceptibility to different malignancies. Not surprisingly, different studies have described a relationship between the presence of 677 C>T and 1298 A>C MTHFR polymorphisms and the leukemia risk development. However, only few studies have reported this issue in CML. For this work, 118 CML patients and 217 controls were studied. The MTHFR 677 C>T and 1298 A>C polymorphisms were investigated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technique. The frequency of CT and TT genotypes of the MTHFR gene (677 C>T) polymorphism in CML patients was significantly higher compared to controls. Moreover, for the AC and CC genotypes of the MTHFR 1298 A>C polymorphism, a statistically highly significant frequency of 1298 CC genotype was also detected in CML patients when compared to control group (OR=1.9, 95%, CI=1.15-3.16, p=0.01, and OR=106.92, 95% CI=14.17-806.64, p=1.7x10(-16), respectively). In addition, CML patients with compound 677CT/1298AC, 677TT/1298AA, 677 CC/1298 AC and 677 CC/1298 CC genotypes were related to a high risk of CML (OR=5.71, 95% CI: 2.751-11.864, p=0.000001; OR=59.5, 95% CI: 12.565-282.071, p=9.8x10(-12), OR=1.9, 95% CI: 0.8678-4.549, p=0.07; OR=206.8, 95% CI: 26.284-1627.034, p=1.15x10(-19) respectively). The frequency of MTHFR 677 C>T and 1298 A>C genotypes was no significantly increased in patients with others phases of CML (accelerated or blastic transformation phases) when compared to the patients in the chronic phase of the disease. We found that both MTHFR 677TT and 1298CC genotypes have been in a high risk to develop a CML in Syrian patients.