亚甲基四氢叶酸还原酶基因多态性对儿童甲氨蝶呤化疗后毒副反应的影响  

The Effect of MTHFR Gene Polymorphism in the Toxic Side Effects of HD-MTX Chemotherapy on Children

作　　者：孟琳懿[1,2] 田怀平[3] 王小洁[1,2] 李红[1,2] 

机构地区：[1]上海市儿童医院 [2]上海交通大学医学院附属儿童医院,上海200040 [3]上海交通大学医学院附属新华医院,上海200092

出　　处：《儿科药学杂志》2013年第2期1-4,共4页Journal of Pediatric Pharmacy

基　　金：上海交通大学医学院科技基金项目(JYY0914)

摘　　要：目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因677C/T和1298A/C的2个SNPs分布对儿童急性淋巴细胞白血病(ALL)患儿接受大剂量甲氨蝶呤(HD-MTX)化疗后毒副反应发生情况的影响。方法:收集43例ALL患儿外周血,提取基因组DNA,用PCR片段直接测序的方法检测MTHFR基因型,观察HD-MTX对患儿产生的毒副反应并评级。结果:MTHFR677CC基因型患儿在粘膜损害、感染、肝损害发生中等以上严重程度的比例高于677CT和677TT型(P<0.05),在胃肠道反应和外周血白细胞减少方面也高于677CT和677TT型,但差异无统计学意义(P>0.05)。MTHFR 1298AC基因型患儿发生中等以上严重程度粘膜损伤的比例高于1298AA基因型(P<0.05),其他方面比较差异均无统计学意义。结论:推测MTHFR基因多态性分布与ALL患儿HD-MTX化疗后发生毒副反应的严重程度有关,携带MTHFR 677CC基因型患儿可能更易发生较严重的毒副反应,临床上可结合疗效考虑用药剂量或做好解救和应对严重毒副反应的措施。Objective： To investigate the effect of the distribution of single-nucleotide polymorphisms （SNPs） of methylenetetrahydrofolate reductase （MTHFR） gene 677C/T and 1298A/C on the occurrence of the toxic side effects on children with acute lymphoblastic leukemia （ALL） after HD-MTX chemotherapy. Methods： Peripheral blood samples of 43 children with ALL were collected ; genomic DNA was extracted ; genotype of MTHFR was detected by direct sequencing of PCR segment. The toxic side effects on patient caused by HD-MTX were observed and rated. Results： The proportions of the occurrence of mucosal damage, infection and liver damage above medium severity in patient with gerotype of MTHFR 677CC were higher than those with CT and rIT （ P〈0.05 ）. This kind of proportional tendency also existed as far as the occurrence of gastrointestinal reaction and leucopenia in peripheral blood, though the differences were of no statistically significance. The proportion of the occurrence of mucosal damage above medium severity in patients with genotype of MTHFR 1298AC was higher than that with 1298AA （P〈0.05） , no significant differences were observed in other aspects of effects and metabolism. Conclusions： The distribution of MTHFR gene polymorphism was inferred to have a relationship with the severity of toxic side effects on patients with .ALL after HD-MTX chemotherapy. Patients carting MTHFR 677CC gene may be more likely to occur with severe toxic side effects. Clinically speaking, based on therapeutic effects, the dosages of anticancer drugs could be adjusted, and more measures could be taken to rescue and cope with severe toxic side effects.

关 键 词：儿童 亚甲基四氢叶酸还原酶 基因 甲氨蝶呤 毒副反应 

分 类 号：R733.7[医药卫生—肿瘤]