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  

Association between ABCC2 genetic polymorphisms and serum concentrations and chemotherapy toxicities of methotrexate in children with acute lymphoblastic leukemia

作　　者：闫安 赵丹琪 王淑梅 YAN An;ZHAO Dan-qi;WANG Shu-mei(Department of Pharmacy,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Department of Clinical Pharmacy,College of Pharmacy,Capital Medical University,Beijing 100069,China;Beijing Key Laboratory of Bio-Characteristic Profiling for Evaluation of Rational Drug Use,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院药学部,北京100038 [2]首都医科大学药学院临床药学系,北京100069 [3]临床合理用药生物特征谱学评价北京市重点实验室,北京100038

出　　处：《中国临床药理学杂志》2024年第5期645-648,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81872926);临床合理用药生物特征谱学评价北京市重点实验室基金资助项目(BZ0439)。

摘　　要：目的 考察急性淋巴细胞白血病(ALL)患儿腺苷三磷酸结合盒亚家族C成员2(ABCC2) rs717620 G>A基因多态性对甲氨蝶呤(MTX)血清浓度和化疗毒性的影响。方法 收集ALL患儿的外周血,提取基因组DNA,用基质辅助激光解吸电离飞行时间质谱技术分析ABCC2 rs717620 G>A基因型,用荧光偏振免疫法测定MTX血清浓度,记录MTX化疗后的ALL复发和毒性发生情况,分析ABCC2 rs717620 G>A基因多态性与剂量校正的MTX浓度(C/D比值)、复发和化疗毒性的相关性。结果 研究共纳入患儿127例,rs717620 GG、GA和AA基因型的分布频率分别为82.68%、16.54%、0.78%;G和A等位基因的分布频率分别为90.94%和9.06%。GG基因型患儿的24 h中位C/D比值(11.94μmol·L^(-1) per g·m^(-2))低于GA和AA基因型患儿(12.64μmol·L^(-1) per g·m^(-2)),中位42 h C/D比值(0.08μmol·L^(-1) per g·m^(-2))高于GA和AA基因型患儿(0.07μmol·L^(-1) per g·m^(-2)),复发率(11.42%)低于GA和AA基因型患儿(18.18%),在统计学上差异均无统计学意义(均P>0.05)。GG基因型患儿的血液毒性发生率(40.95%)和电解质紊乱发生率(21.90%)显著高于GA和AA基因型患儿(分别为13.64%和0.00%,P<0.05),其余不良事件的发生率在统计学上差异均无统计学意义(均P>0.05)。结论 ABCC2 rs717620 GG基因型可能是ALL患儿发生血液毒性和电解质紊乱的危险因素。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 127children 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 medianC/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(allP>0.05).Conclusion ABCC2 rs717620 GG might be a risk factor for hematological and electrolyte disorders in ALL children treated with MTX.

关 键 词：甲氨蝶呤 急性淋巴细胞白血病 腺苷三磷酸结合盒亚家族C成员2 基因多态性 

分 类 号：R97[医药卫生—药品]