儿童急性白血病化疗药物相关基因多态性谱初绘及与国外人群的对比分析

Preliminary mapping of chemotherapy drug related genetic polymorphism spectrum in children with acute leukemia and comparative analysis with foreign populations

关键词:  药物基因组学  单核苷酸多态性  个体化用药  儿童白血病

Key words:  Pharmacogenomics  Single nucleotide polymorphism  Individualized medication  Childhood leukemia

摘要:

目的:探讨儿童白血病化疗药物相关单核苷酸多态性(SNPs)分布特征,为临床个体化用药提供参考。方法: 对2018年1月至2020年12月初诊儿童急性白血病患者骨髓样本进行二代测序及SNP分析,比较等位基因和基因型频率分布差异,评估Hardy-Weinberg平衡,并与国外数据对比。结果:检测6类抗肿瘤药物涉及的26个基因位点,仅NUDT15(415C>T)和TP53(215G>C)不符合Hardy-Weinberg平衡,其余位点SNPs频率与东亚人群基本一致。NUDT15(415C>T)在本研究和东亚更常见；GSTP1(313A>G)在欧美人中突变频率较高；MTHFR(665G>A)各人群间差异不大。结论:中国儿童白血病患者药物相关SNPs分布具有特点,临床应结合本土基因特征实施个体化用药。

Abstract:

OBJECTIVE To investigate the distribution characteristics of single nucleotide polymorphisms (SNPs) associated with chemotherapy drugs in pediatric leukemia patients and offer a reference for clinical personalized medication. METHODS Second - generation sequencing and SNP analysis were conducted on bone marrow samples obtained from pediatric patients diagnosed with acute leukemia between January 2018 and the beginning of December 2020. The frequency distribution disparities of alleles and genotypes were compared, the Hardy - Weinberg equilibrium was assessed, and cross - referencing with international data was carried out. RESULTS Among the 26 genetic loci associated with six categories of anti - tumor drugs detected, only NUDT15 (415C>T) and TP53 (215G>C) deviated from the Hardy - Weinberg equilibrium, whereas the frequencies of other SNPs were in accordance with those in East Asian populations. NUDT15 (415C>T) was more prevalent in this study cohort and East Asia; GSTP1 (313A>G) presented higher mutation frequencies in European and American populations; MTHFR (665G>A) showed minimal population - specific variations.CONCLUSION Drug - related SNPs in Chinese pediatric leukemia patients display distinct distribution patterns, and clinical personalized medication should be implemented in accordance with local genetic characteristics.