亚甲基四氢叶酸还原酶基因的多态性对白血病治疗的意义

Significance of Methylene Tetrahydrofolate Reductase Gene Polymorphism in Treatment of Leukemia

目的研究亚甲基四氢叶酸还原酶基因多态性与急性淋巴白血病患者化疗不良反应之间的关系。方法选取2018年9月至2019年6月重庆市巫山县人民医院收治的急性淋巴白血病完全缓解期患者31例,确认患者DNA的基因型,监测化疗过程中的不良反应,研究分析亚甲基四氢叶酸还原酶基因表型与化疗不良反应的关系。结果亚甲基四氢叶酸还原酶中的C677T基因型中包括CC型(表示酶活性100%),CT型(表示酶活性65%),TT型(表示酶活性30%),其中CC型与以下不良反应具有密切的关系,包括:中性粒细胞数量的减少;黏膜出现损伤的情况;肝毒性的产生情况,其他两种基因型,CT型、TT型与不良反应无明显关系,CC型患者的中性粒细胞数量减少患者有17例,黏膜损害患者有16例,肝毒性患者有8例,血红蛋白水平减少有4例,血小板数量减少患者有3例,胃肠道反应为8例,CT型患者中性粒细胞数量减少患者有5例,黏膜损害患者有4例,肝毒性患者有1例,血红蛋白水平减少有1例,血小板数量减少患者有1例,胃肠道反应为6例,TT型患者中中性粒细胞数量减少患者有4例,黏膜损害患者有4例,肝毒性患者有1例,血红蛋白水平减少有2例,血小板数量减少患者有1例,胃肠道反应为7例。结论白血病患者在进行大剂量的化疗过程中,C677T基因型中的CC型基因型患者有可能出现中性粒细胞减少、黏膜损伤、肝毒性等不良反应,说明甲氨喋呤基因的多态性与白血病的治疗具有密切的关系。

Objective To study the relationship between methylenetetrahydrofolate reductase gene polymorphism and adverse effects of chemotherapy in patients with acute lymphoblastic leukemia.Methods From September 2018 to June 2019,31 patients in complete remission stage of acute lymphoblastic leukemia admitted to Wushan County People's Hospital of Chongqing were selected to confirm their DNA genotypes and monitor adverse reactions during chemotherapy.To study the relationship between the phenotype of methylenetetrahydrofolate reductase gene and adverse effects of chemotherapy.Results The C677T genotypes in methylene tetrahydrofolate reductase included CC genotypes(indicating enzyme activity of 100%),CT genotypes(indicating enzyme activity of 65%)and TT genotypes(indicating enzyme activity of 30%).The appearance of mucosal injury;Hepatotoxicity producing situation,the other two genotypes,CT,TT has no obvious relation with adverse reactions,CC type to reduce the number of neutrophils in patients with 17 cases,16 patients with mucosal injury,8 patients with liver toxicity,hemoglobin levels decrease in 4 cases,3 patients with the decrease in the number of platelets,gastrointestinal reaction for 8 cases,CT in patients with type patients with the decrease in the number of neutrophils in 5 cases,4 patients with mucosal damage,patients with hepatic toxicity in 1 case,hemoglobin levels decrease in 1 case,patients with the decrease in the number of platelets in 1 case,gastrointestinal reaction for 6 cases,Among the TT patients,4 had decreased neutrophils,4 had mucosal damage,1 had hepatotoxicity,2 had decreased hemoglobin,1 had decreased platelet count,and 7 had gastrointestinal reactions.Conclusion During the highdose chemotherapy of leukemia patients,CC genotypes in the C677T genotype are likely to have adverse reactions such as neutropenia,mucosal damage and hepatotoxicity,indicating that the methotrexate gene Polymorphism is closely related to the treatment of leukemia.