Impact of Methionine Synthase Reductase Polymorphisms in Chronic Myeloid Leukemia Patients

Abstract

Introduction： Metabolism methionine and of folate play a vital function in cellular methylation reactions, DNA synthesis and epigenetic process.However, polymorphisms of methionine have received much attention in recent medical genetics research. Objectives: To ascertain whether the common polymorphisms of the MTRR (Methionine Synthase Reductase) A66G gene could play a role in affecting susceptibility to Chronic Myeloid Leukemia (CML) in Sudanese individuals. Methods: In a case-controlled study, we extracted and analyzed DNA from 200 CML patients and 100 healthy control subjects by the PCR-RFLP method. Results: We found no significant difference in age orgender between the patient group and controls. The MTRR A66G genotypes were distributed based on the Hardy-Weinberg equilibrium (p > 0.05). The variation of MTRR A66G was less significantly frequent in cases with CML (68.35%) than in controls (87%) (OR = 0.146, 95% CI = 0.162−0.662, p < 0.002). Additionally, AG and GG genotypes and G allele were reducing the CML risk (Odds ratio [OR] = 0.365; 95% CI [0.179−0.746]; p = 0.006; OR = 0.292; 95% CI [0.145−0.590]; p = 0.001 and OR = 0.146; 95% CI [0.162−0.662]; p = 0.002 and OR = 2.0; 95% CI [1.3853−2.817]; respectively, (p = 0.000)). Conclusions: Our data demonstrated that heterozygous and homozygous mutant genotypes of MTRR polymorphisms were associated with decreased risk of developing CML in the Sudanese population.

Keywords: CML; MTRR; Sudanese population; folate and genetic polymorphism.

Figure 1

Representative PCR products and PCR-RFLP analysis of MTRR A66G. (a) PCR products of MTRR A66G: Lane 1 is a 50 base-pair ladder. Lanes 2–7 and 8 show the 66 bp PCR products. (b) PCR-RFLP analysis of MTRR A66G polymorphism using Nde1I restriction enzyme: Lane 1depicts the DNA molecular weight marker with a 50 base-pair ladder. Lanes 2, 4, and 7 show Homozygous wild-type (AA) one band at 44 bp (band 22 bp didnot appear due to its small molecular size). Lane 3 shows the Heterozygous (AG) two bands 66 and 44(also band 22 bp didnot appear due to its small molecular size). Lanes 5 and 6 show a Homozygous mutant (GG) one band 66 bp.