亚甲基四氢叶酸还原酶基因多态性与儿童急性淋巴细胞白血病风险的相关性研究

摘要

目的 探讨中国汉族儿童亚甲基四氢叶酸还原酶(MTHFR)基因的单核甘酸多态(MTHFR 677C→T及1298 A→C突变)对儿童急性淋巴细胞白血病(ALL)发病风险的影响.方法 收集176例ALL患儿以及与其匹配的170例对照者外周血,通过多重单碱基延伸反应(SNaPshot SNP分型技术)检测MTHFR C677T和A1298C基因型.结合临床资料,比较不同基因型对儿童ALL发病风险的影响及与临床危险度的相关性.结果 MTHFR C677T位点和MTHFR A1298C位点的各基因型在病例组与对照组间分布差异无统计学意义.兼具二种突变的基因型677CT/1298AC分布频率在病例组与对照组间分布差异无统计学意义.MTHFR C677T基因多态性在临床危险度分型及复发组中分布差异有统计学意义.MTHFR 677基因型TT在标危组中占43.0%,高于中危、高危及复发组的频率(P ＜ 0.01).MTHFR 677基因型CC在标危组中占24.0%,低于中危、高危及复发组的频率(P ＜ 0.05).结论 MTHFR 677基因型与儿童ALL的临床危险度分型和复发相关.MTHFR基因677C→T突变可能对中国儿童ALL有一定保护性作用.%Objective To investigale the relationship between genetic polymorphism (677C→T and 1298 A→C) of methylenetetrahydrofolate reductase (MTHFR) and the risk of childhood acute lymphocytic leukemia (ALL).Methods A total of 176 patients with ALL and a cohort of 170 matched healthy children were included. DNA was extrac:ted from their peripheral blood. SNaPshot SNP typing was used to determine the genotypes of MTHFR C677T and A1298C. Combined with clinical data, the relationship between genetic polymorphism of MTHFR and the risk of childhood ALL was analyzed. Results No significant association betw eeu the MTHFR C677T polymorphism or A1298C polymorphism and the risk of leukemia. No evidence of an association with MTHFR 677CT/1298AC was observed for ALL. The MTHFR C677T variant allele had statistically significant association with the clinical classification of acute leukemia-related degree and relapse. The frequency of the MTHFR 677TT in the standard risk group (43.0％) is higher than the other groups (P＜0.01). The frequency of the MTHFR 677CC in the standard risk group (24.0％) is lower than the other groups (P＜0.05). Conclusions MTHFR C677T may be related to the clinical classification of acute leukemia-related degree. The MTHFR 677C →T polymorphism may be a genetic protective factor for childhood acute lynmphocytic leukemia in China.