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

摘要

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 withALL 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 mutauon 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.%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MTHFRC677T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).MTHFRC677T、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.