Association between the methylenetetrahydrofolate reductase gene polymorphisms and haplotype with toxicity response of high dose methotrexate chemotherapy / 中华流行病学杂志

ABSTRACT

Objective To investigate the association between single nucleotide polymorphisms (SNP) and its haplotypes of methylenetetrahydrofolate reductase (MTHFR) gene with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastie leukemia (ALL).Methods HDMTX-treated children with ALL (1.2 to 14-years old) were selected from inpatient and followed for a retrospective study.The toxicity response of HDMTX chemotherapy was evaluated using WHO common toxicity criteria.Sixty-one patients with therapy-related toxicity and 36 patients without therapy-related toxicity were genotyped for 2 ShP (677C＞T and 1298A＞C) of the MTHFR gene by polymerase chain reaction-restriction fragment length polymorphism.Frequency of haplotypes and linkage disequilibrium of MTHFR gene were analyzed by SHEsis program.Results The distribution of MTHFR gene 677C＞T polymorphism did not appeare different between groups with or without toxicity response (x2=4.609,P=0.100),but the 1298A＞C polymorphism was significantly different (x2=10.192,P=0.006).Individuals who carried C allele (AC +CC genotype) had a decreased risk of toxicity response compared to AA genotype ( OR=0.245,95％CI0.099-0.607,P=0.002).677C＞T and 1298A＞C polymorphisms showed strong linkage disequilibrium (D'=0.895 ).The CC haplotype was significantly associated with decreased risk of toxicity response (OR=0.338,95％CI0.155-0.738,P=0.005),while the TA haplotype was significantly associated with the increased risk of toxicity response (OR=1.907,95％ CI1.045-3.482,P=0.035).Conclusion MTHFR gene 1298C allele and CC haplotype might serve as protective factors while TA haplotype as a risk factor for the susceptibility to toxicity response of HDMTX chemotherapy in children with ALL.