MTHFR及TPMT基因多态性对儿童急性淋巴细胞白血病化疗不良反应的影响  

Influence of single nucleotide polymorphism of MTHFR and TPMT on adverse reactions of chemotherapy in children with acute lymphocytic leukemia

作　　者：齐兴菊[1] 冯杰[1] QI Xingju;FENG Jie(Department of Pediatrics,Guizhou Provincial People′s Hospital,Guiyang,Guizhou 550002,China)

机构地区：[1]贵州省人民医院儿科,贵阳550002

出　　处：《重庆医学》2018年第10期1343-1346,1350,共5页Chongqing medicine

摘　　要：目的探讨亚甲基四氢叶酸还原酶(MTHFR)及巯嘌呤甲基转移酶(TPMT)单核苷酸基因多态性(SNP)对急性淋巴细胞白血病(ALL)儿童化疗后不良反应的影响。方法选择2014年1月至2016年10月对该院儿内血液科收治的98例ALL患儿,采用梯度PCR及DNA测序技术,检测MTHFR C677T、A1298C及TPMT A719G、G460A的基因型,比较不同SNP与化疗后不良反应的关系。结果 ALL患儿MTHFR C677T和A1298C的突变率分别为66.33%和44.90%,TPMT A719G、G460A的突变率分别为12.24%及9.18%。MTHFR A1298AC发生血小板降低的比例(28.13%)高于A1298AA基因型(7.41%)与A1298CC基因型(8.33%),比较差异有统计学意义(P<0.05)。MTHFR A1298AA发生黏膜损伤的比例(9.26%)低于A1298AC基因型(43.75%)与A1298CC基因型(50.00%),比较差异有统计学意义(P<0.05)。MTHFR C677T、TPMT A719G、G460A等基因型与化疗后不良反应比较差异均无统计学意义(P>0.05)。结论MTHFR A1298C与ALL患儿MTX化疗后不良反应的发生有关。Objective To investigate the influence of single nucleotide polymorphism(SNP)of methylenetetrahydrofolate reductase(MTHFR)and thiopurine S-methyltransferase(TPMT)on adverse reactions of chemotherapy in children patients with acute lymphocytic leukemia(ALL).Methods Ninety-eight children patients with ALL in the pediatric department of this hospital from Jan.2014 to Dec.2016 were chosen.The gradient PCR and DNA sequencing were adopted to detect the genotypes of MTHFR C677T,A1298C and TPMT A719G,G460A.The relationships between different SNP with adverse reactions were compared.Results The mutation rates of MTHFR C677T and A1298C were 66.33%and 44.90%respectively,which of TPMT A719G and G460A were 12.24%and 9.18%respectively.The proportion of MTHFR A1298AC developing thrombocytopenia was 28.13%,which was higher than 7.41%of those carrying A1298AA and 8.33%of those carrying A1298CC,the difference was statistically significant(P<0.05).The proportion of MTHFR carrying A1298AA developing mucosal injury was 9.26%,which was lower than 43.75%of those carrying A1298AC and 50.00%of those A1298CC(P<0.05).The differences in the genotypes of MTHFR C677T,TPMT A719G and TPMT G460A and the adverse reactions after chemotherapy were not statistically significant(P>0.05).Conclusion The MTHFR A1298C polymorphism might be associated with the adverse reactions of MTX chemotherapy in ALL children.

关 键 词：急性淋巴细胞白血病 儿童 亚甲基四氢叶酸还原酶 巯嘌呤甲基转移酶 不良反应 

分 类 号：R725.5[医药卫生—儿科]