Methylenetetrahydrofolate Reductase (MTHFR) Genotype Association with the Risk of Chronic Myelogenous Leukemia

Said I. Ismail, Nida A. Ababneh, Abdallah Awidi

Abstract


The metabolism of folate is essential in DNA synthesis, and polymorphisms of genes involved in this metabolism have been implicated in many types of cancer. One such gene is the Methylenetetrahydrofolate Reductase (MTHFR) gene, which encodes an enzyme that converts folate to a methyl donor used for DNA methylation. In this report, we studied the association between the different genotypes of the two most common MTHFR polymophisms, C677T and A1298C, and the risk of Chronic Myelogenous Leukemia (CML). For this purpose, 149 of previously diagnosed CML patients and 170 normal controls were examined using PCR followed by Restriction Fragment Length Polymorphism (RFLP). Results showed that the frequency of the C677T TT homozygous mutant genotype in patients with CML was significantly higher compared to controls (OR = 2.84, 95% CI: 1.24-6.50, P-value = 0.014). No such association was shown for the heterozygous C677T CT genotype (OR = 1.52, 95% CI: 0.95-2.41, P-value = 0.081). As for the A1298C genotypes, a statistically significant higher frequency of the mutant homozygous genotype 1298CC was also detected in CML patients compared to the control group (OR = 2.18, 95% CI: 1.01-4.69, P-value = 0.046). No such statistical significance was demonstrable for the heterozygote genotype 1298AC (OR = 1.08, 95% CI: 0.68-1.73, P-value = 0.743). This is the first report to suggest that both mutated MTHFR genotypes, specifically the homozygous 677TT and 1298CC polymorphisms, can be associated with a higher risk of developing CML.

Keywords


CML, MTHFR, C677T, A1298C

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