RFC1基因多态性与大剂量甲氨蝶呤治疗反应的相关性  

Correlation between genetic polymorphism of RFC1 gene and therapeutic reaction of high dose methotrexate

作　　者：李红[1,2] 蒋慧[1,2] 刘青[1,2] 

机构地区：[1]上海市儿童医院 [2]上海交通大学附属儿童医院血液科,上海200040

出　　处：《上海交通大学学报（医学版）》2014年第9期1376-1380,共5页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市科委重大课题子项目(14411950602)~~

摘　　要：目的研究RFC1 G80A基因多态性与儿童急性淋巴细胞白血病(ALL)大剂量甲氨蝶呤(HDMTX)治疗反应的关系。方法以接受HDMTX(剂量>1 g/m^2)治疗的68例患儿(280例次)作为研究对象。MTX治疗前检测RFC1 G80A基因多态性;定时测定血浆MTX浓度和肝肾功能、血常规,观察MTX相关毒副反应及预后,评估其相关性。结果 RFC1 G80A基因多态性与MTX毒副反应相关,AA基因型发生中重度肝脏损害及骨髓抑制的风险分别是GG型7.28倍和2.8倍(P=0.000,0.005),可以作为预测HDMTX毒副反应的危险指标。RFC1 G80A各基因型MTX排泄延迟发生和预后的差异无统计学意义(P>0.05)。结论 RFC1G80A基因多态性与HDMTX治疗后中重度肝脏损害及骨髓抑制的发生相关,可以作为预测HDMTX毒副反应的危险指标。Objective To investigate the correlation of genetic polymorphism of RFC1G80A and the therapeutic reaction of high dose methotrexate （HDMTX） for treating the childhood acute lymphoblastic leukemia （ALL）. Methods Sixty-eight patients （280 case-times） treated by HDMTX （dose 〉1 g/m2） were selected. The genetic polymorphism of RFC1 G80A was detected before MTX treatment. Plasma MTX level, liver and kidney function, and peripheral blood cell count were detected regularly. Toxic side effects of MTX and prognosis were observed and their correlation was evaluated. Results The genetic polymorphism of RFC1 GSOA was correlated with toxic side effects of MTX. The risks of moderate and severe hepatotoxicity and myelosuppression of RFC1-AA genotype were 7.28 and 2.8 times higher than those of RFC1-GG genotype （/9=0. 000, 0. 005）, therefore RFC1-AA genotype was a risk indicator for predicting toxic side effects of HDMTX. The differences of elimination delay of MTX and prognosis of genotypes of RFC1 G80A were not statistically significant （P 〉 0.05）. Conclusion The genetic polymorphism of RFC1G80A is correlated with moderate and severe hepatotoxicity and myelosuppression after HDMTX treatment and can be used as a risk indicator for predicting toxic side effects of HDMTX.

关 键 词：甲氨蝶呤 还原叶酸载体 药物浓度 毒副反应 急性淋巴细胞白血病 儿童 

分 类 号：R733.71[医药卫生—肿瘤]