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还原性叶酸载体基因多态性与大剂量甲氨蝶呤化疗反应的关系分析 被引量:4

Relationship between Polymorphism of Reduced Folate Carrier Gene with Chemotherapy Response to High Dose Methotrexate
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摘要 目的研究还原性叶酸载体(RFC1)基因多态性与大剂量甲氨蝶呤(HD-MTX)化疗反应的关系。方法选取我院2016年8月—2018年4月收治的急性淋巴细胞白血病(ALL)患儿90例,提取患儿血液DNA后检测其RFC1 80位点基因型,比较AA、AG+GG基因型患儿在HD-MTX治疗后化疗反应发生率,分析RFC1 G80A基因多态性与HD-MTX治疗后化疗反应发生的关系,测定不同基因型患儿化疗48 h后血药浓度,比较AA型、AG+GG型患儿与HD-MTX排泄延迟的关系。结果本组AA型24例、AG型45例、GG型21例,AA型患儿骨髓抑制、肝功能损伤、排泄延迟率发生的风险高于AG+GG型(P<0.05),AA型与AG+GG型患儿口腔黏膜炎和消化道反应发生率均无统计学意义(P>0.05)。结论 ALL患儿RFC1 G80A基因多态性与HD-MTX化疗反应存在相关性,可能成为预测HD-MTX化疗反应的遗传学标记。 Objective To study relationship between polymorphism of reduced folate carrier (RFC1) gene with chemotherapy response to high dose Methotrexate (HD-MTX). Methods Blood DNA of 90 children with acute lymphoblastic leukemia (ALL) admitted during August 2016 and April 2018 were extracted. RFC1 80 locus genotypes in children were detected. Incidence rate of chemotherapy response in children with AA and AG+GG genotypes after HD-MTX treatment was compared, and relationship between RFC1 G80A gene polymorphism with chemotherapy response after HD-MTX treatment was analyzed. Plasma concentrations of children with different genotypes after chemotherapy for 48 h were detected, and relationship between children with AA and AG+GG types with HD-MTX deferred excretion was analyzed. Results There were 24 children with AA type, 45 children with AG type and 21 children with GG type. Risk values of bone marrow depression, liver function damage and deferred excretion in children with AA type were significantly higher than those in children with AG + GG type ( P <0.05). There were no significant differences in incidence rates of oral mucositis and digestive tract reaction between children with AA and AG+GG genotypes ( P >0.05). Conclusion There is a correlation between RFC1 G80A gene polymorphism and HD-MTX chemotherapy response in children with ALL, which may be a genetic marker for predicting HD-MTX chemotherapy response.
作者 崔毅佳 王淑梅 金志国 CUI Yi-jia;WANG Shu-mei;JIN Zhi-guo(Department of Pharmacy, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China;Beijing Key Laboratory of Clinical Rational Administration Bioavailability Spectroscopy Evaluation, Beijing 100038, China;International Cooperation and Joint Laboratory of Clinical Rational Administration Bioavailability Spectroscopy Evaluation, Beijing 100038, China)
出处 《解放军医药杂志》 CAS 2019年第5期35-38,共4页 Medical & Pharmaceutical Journal of Chinese People’s Liberation Army
基金 国家自然青年科学基金项目(81503135)
关键词 白血病 淋巴样 还原性叶酸载体基因 多态性 甲氨蝶呤 药物毒性 Leukemia, lymphoid Reduced folate carrier gene Polymorphism Methotrexate Drug toxicity
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