急性淋巴细胞白血病患儿ABCC2基因多态性与甲氨蝶呤血清浓度和化疗毒性的相关性研究OA北大核心CSTPCD

Objective To investigate the effects of adenosine triphosphate-binding cassette,sub-family C,member 2(ABCC2)rs717620 G＞A polymorphisms on serum concentrations and chemotherapy toxicities of methotrexate(MTX)in children with acute lymphoblastic leukemia(ALL).Methods Peripheral blood samples were obtained from children with ALL to extract genome DNA.Matrix-assisted laser desorption/ionization time of flight mass spectrometry was used to detect the genotypes of ABCC2 rs717620 G＞A polymorphisms.Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX.The incidences of ALL relapse and toxicities were recorded after chemotherapy with MTX.The associations of ABCC2 rs717620 G＞A polymorphisms with dose-adjusted serum concentrations(C/D ratios),relapse,and chemotherapy toxicities of MTX were analyzed.Results A total of 127 children were included in the present study.The frequencies of rs717620 GG,GA and AA genotypes were 82.68％,16.54％and 0.78％,respectively.The frequencies of G and A alleles were 90.94％and 9.06％,respectively.Children with the GG genotype had lower median C/D ratios of MTX in 24 h(11.94 μmol·L-1 per g·m-2),higher C/D ratios of MTX in 42 h(0.08 μmol·L-1 per g·m-2),and lower relapse rates(11.42％)than those in GA and AA genotype carriers(12.64 and 0.07 μmol·L-1 per g·m-2,and 18.18％,respectively).However,none of the above differences were statistically significant.The incidences of hematological(40.95％)and electrolyte disorders(21.90％)in children with the GG genotype were significantly higher than those in GA and AA genotype carriers(13.64％and 0.00％,respectively,P＜0.05).There were no statistically significant differences in the incidences of other adverse events between patients with the GG genotype and patients with the GA and AA genotypes(all P＞0.05).Conclusion ABCC2 rs717620 GG might be a risk factor for hematological and electrolyte disorders in ALL children treated with MTX.