急性淋巴细胞白血病患儿还原叶酸载体基因多态性与甲氨蝶呤不良反应的关系  

Association between genetic polymorphism of RFC1 and methotrexate-induced toxicity in children with acute lymphoblastic leukemia

作　　者：杨丽华[1] 余晶[1] 邓兰[2] 杜江[1] 王斌[1] 

机构地区：[1]南方医科大学珠江医院儿科,广东广州510282 [2]南方医科大学珠江医院血液内科,广东广州510282

出　　处：《临床儿科杂志》2011年第5期425-428,共4页Journal of Clinical Pediatrics

基　　金：广东省自然科学基金博士启动项目(No.8451051501000516)

摘　　要：目的研究还原叶酸载体基因(RFC1)A80G多态性对急性淋巴细胞白血病(ALL)患儿使用大剂量甲氨蝶呤(HDMTX)化疗的不良反应以及甲氨蝶呤(MTX)排泄延迟的影响。方法筛选ALL患儿40例,提取其基因组DNA,用DNA直接测序法检测RFC1 80位点基因型,观察所有患儿经HDMTX化疗后的不良反应,并应用荧光偏振免疫分析法(FPIA)测定MTX血药浓度。结果 ALL患儿在HDMTX化疗中,RFC1 80AA基因型者骨髓抑制发生的风险是GG基因型者的8.67倍(OR=8.67,95%CI:1.05～71.57,P=0.045);RFC1 A80G基因型与肝脏损害无明显相关,与MTX排泄延迟亦无明显相关。结论 RFC1 80位基因型可能成为预测ALL患儿HDMTX化疗不良反应的有效遗传学标记,值得进一步进行功能学探讨及大样本人群验证。Objective To investigate the association between gene polymorphism of reduced folate carrier （RFCI） A80G and toxicity and delayed elimination of high dose methotrexate （HDMTX） in childhood acute lymphoblastic leukemia （ALL）. Methods A total of 40 children with ALL were selected. DNA was extracted from their peripheral blood. Direct DNA sequencing was applied to detect the genotypes of RFC1-A80G. The toxicity response of patients received HDMTX chemotherapy was observed, and fluorescence polarization immunoassay was applied to determine the plasma concentration of MTX. Results During the HDMTX chemotherapy for childhood ALL, the incidence rate of myelosuppression was 8.67-fold higher in carriers of RFC1 80AA genotype as compared with patients with 80GG genotype （OR = 8.67, 95% CI： 1.05 - 71.57, P = 0.045） ; the RFC1 A80G polymorphism had neither significant correlation with the incidence rate of hepatotoxicity induced by HDMTX, nor with the incidence rate of delayed elimination. Conclusions The genotype of RFC1 80 may be an effective genetic marker to predict HDMTX induced toxicities in childhood ALL, further functional studies in large sample population are needed.

关 键 词：急性淋巴细胞白血病 还原叶酸载体 基因多态性 甲氨蝶呤 不良反应 

分 类 号：R733.71[医药卫生—肿瘤]