Gene polymorphisms investigation of methylenetetrahydrofolate reductase (MTHFR) enzyme at chronic lymphocytic leukemia (CLL)

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. In the current study, MTHFR gene A1298C (rs1801131) and C677T (rs1801133) polymorphisms were investigated in a case–control study of 91 patients with chronic lymphocytic leukemia (CLL) and 101 healthy control subjects by using a real-time polymerase chain reaction (RT-PCR). The allele and genotype frequencies of MTHFR gene A1298C polymorphism were compared between control and case groups. In the statistical analysis, the A allele and AA genotype were significantly found to be protective variant. There were significant associations between the control and the case groups for the C allele and CC genotype of A1298C polymorphism (p=0.04 and p=0.03). The 1298CC genotype increased 2.58-fold the risk of CLL. The allele and genotype frequencies of MTHFR gene C677T polymorphism were compared between control and case groups. There was no association between the control and the case groups for the allele frequencies of C677T polymorphism. However, in the statistical analysis, 677CT and 677CC genotypes significantly increased the risk of CLL (P=0.04, OR=4,21 (1,10-16,09) and P=0.05, OR=3,77 (1,00-14,17), respectively). When the haplotype analysis was performed, there were significant differences between the case and control groups in terms of haplotype blocks. The AC haplotype block (A1298 ve C677) showed a protective effect against the risk of CLL (p=0.034). Our results demonstrate that MTHFR gene 1298C and C677 alleles have a major effect on the risk of CLL.