Detection of Genetic polymorphisms of Methylene tetrahydrofolate reductase among Sudanese patients with chronic myeloid leukemia

Background: Methylenetetrahydrofolate reductase (MTHFR) plays a crucial part in cellular biochemistry because it is involved in the metabolism of the folate critical to DNA synthesis. Aim: To evaluate gene polymorphisms in MTHFR and the susceptibility to chronic myelocytic leukemia (CML). Methods: Two hundred CML cases were included in this study, plus one hundred healthy volunteers as controls. All participants were genotyped for both the A1298C and C677T polymorphisms of MTHFR. Results: Presence of the
77CC/1298AA (wild-type) group was the observational benchmark for the study. The frequency of heterozygous 677CT in CML patients was significantly higher than in the control group [23.5 vs 0.5% (p value = 0.000)], and it imparted a significant risk in CML development. No comparable association was found for homozygous 677TT (OR=1.514, 95% CI: 0.809-2.835, p=1.95). For the 1298 A>C polymorphism, a significant variation in the prevalence of the 1298AC genotype between CML patients and controls was found [55% vs 44% (p=0.006)]. However, the frequency of the 1298CC genotype was higher in CML patients (11%) in comparison with the controls (0%), (p=0.006). Also, both the MTHFR 1289AC and 1298CC genotypes were considered as genetic factors which increased the risk of CML. Furthermore, genotypic analysis revealed the following four combinations correlating to an elevated risk of CML: 677CC/1298CC, 677CT/1298AA, 677CT/1298AC and 677TT/1298AC. Conclusions: This study found evidence of an association between CML in Sudanese patients and the C677T and A1298C polymorphisms of the MTHFR gene.