Significance Of The Expression Of Folic Acid Metabolism Key Enzyme Genetic Polymorphism In Childhood Acute Leukemia

Objective:To detect the frequency distribution patterns of genotype polymorphism of reduced folate carrier (RFC1)G80A methylenetetrahydrofolate reductase (MTHFR)gene C677T and A1298C; 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC)gene C347G in acute leukemia patients and control group,to explore whether these mutation is related to the susceptibility of childhood acute lymphoblastic leukemia and prognosis;to collect clinical data of patients with acute lymphoblastic leukemia during high-dose MTX,to combine these genotypes in patients with the distribution of genetic polymorphism on MTX reasonable clinical safety of individualized medication guide.MethodsTo detect the frequency distribution patterns of genotype polymorphism of RFC1 G80A,MTHFR C677T,MTHFR A1298C,ATIC C347G genotypen,in 176 cases of children with acute lymphoblastic leukemia patients and 170 healthy control individuals,by using SNaPshot SNP typing detected in case - control study and record the clinical data of case group and the control group,and collect clinical data of 164 patients during high-dose MTX chemotherapy. Statistics of four genotypes and susceptibility to acute lymphoblastic leukemia,risk,immunophenotype and prognosis,and draw the survival curves of the recurrent group with different genotypes. Statistical analysis of genotype distribution of MTX toxicity(MTX plasma concentrations decreased latency,liver and kidney dysfunction,mucosal damage,rash,leukopenia and gastrointestinal reactions) relationship.Results:1. RFC1 G80A, MTHFR C677T, MTHFR A1298C, ATIC C347G genotype in acute lymphocytic leukemia group and control group, acute lymphocytic leukemia among different immunophenotype in acute lymphocytic leukemia in children with long-term survival are not significantly different distribution. RFC1 G80A, MTHFR A1298C, ATIC C347G genotype in the clinical risk classification and recurrence in patients with no significant difference in the distribution. MTHFR C677T gene polymorphism typing of clinical risk and relapse patients there is significant difference in the distribution, MTHFR C677T genotype CC in acute lymphocytic leukemia relapse group accounted for 52.4%, higher than the standard, medium and high-risk group (P <0.05) . MTHFR C677T genotype TT in the standard risk group, 43.0%, higher than in the frequency of high-risk and recurrent group (P <0.05). The allele frequency in each group showed no significant difference.2. RFC1 G80A genotype and allele G and A in accordance with HD-MTX chemotherapy of mucosal damage, gastrointestinal reactions and neutropenia, rash, infection level of grouping, and the toxicity of the distribution of points with significant differences. RFC1 G80A GG genotype of the MTX plasma concentrations decreased significantly faster than other genotypes, allele G of the MTX plasma concentrations decreased significantly faster than the allele A. RFC1 G80A GA genotype and renal damage have not occurred and the frequency of patients with significantly higher frequency of allele G and A are no significant differences.3. MTHFR A1298C genotype in HD-MTX chemotherapy, mucosal damage of the frequency distribution of groups are significantly different: genotype AC in severe mucosal injury significantly increased the frequency of genotype AA did not occur in significantly higher frequency of mucosal damage. MTHFR A1298C genotype in HD-MTX chemotherapy, other side effects of the frequency distribution of groups with no significant difference. MTHFR A1298C allele A and C groups in various side effects and toxicity of points in the frequency of no significant difference.4. MTHFR C677T genotypes in the HD-MTX chemotherapy secondary infection, mucosal damage, liver and kidney dysfunction, gastrointestinal reactions, leukopenia, skin rash, MTX plasma concentrations fall time, and toxicity of group frequency distribution of points have a significant difference in the frequency of TT genotype than in the no side effects occurred significantly higher in patients. MTHFRC677T allele C and T in the HD-MTX chemotherapy secondary infection, mucosal damage, renal dysfunction and leukopenia, skin rash, MTX plasma concentrations fall time of the frequency distribution of all groups are significantly different, T allele no more side effects occurred in patients is significantly higher in frequency. MTHFRC677T allele C and T levels in the gastrointestinal tract, the frequency distribution of groups no significant difference.5. In the HD-MTX chemotherapy secondary to severe infection of the patients are ATIC C347G GG genotype patients is significantly higher than other genotypes, the distribution of allele frequency of G allele is significantly higher than C. ATIC C347G genotype in HD-MTX chemotherapy secondary to mucosal injury, MTX plasma levels decreased, liver and kidney dysfunction, gastrointestinal reactions and neutropenia, rash, and toxicity of the distribution of integral group showed no significant difference in allele G and C is not a significant difference.Conclusion:1. there is no apparent connection between RFC1 G80A,MTHFR A1298C,ATIC C347G gene polymorphisms and acute leukemia's susceptibility,immune type,clinical grading.2. MTHFR C677T and the risk of acute leukemia type are related. RFC1 G80A, MTHFR A1298C, ATIC C347G gene polymorphisms and risk of acute leukemia classification are no significant correlation3. RFC1 G80A , MTHFR A1298C , MTHFR C677T,ATIC C347Ggene polymorphism may be related to high-dose MTX chemotherapy-related side reactions...