Oliveira Elisabete, Alves Sandra, Quental Sofia, Ferreira Fátima, Norton Lucília, Costa Vitor, Amorim António, Prata Maria João
Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
J Pediatr Hematol Oncol. 2005 Aug;27(8):425-9. doi: 10.1097/01.mph.0000177513.81465.94.
Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metabolism and in DNA methylation and synthesis. The role of two common polymorphisms at the MTHFR gene, C677T and A1298C, in the etiology of childhood or adult acute lymphoblastic leukemia (ALL) has been previously investigated. Although a protective effect of MTHFR677T against ALL was systematically reported, the magnitude of the effect appeared to be influenced by population-specific gene-environmental interactions. The evidence of the role of MTHFR1298C in ALL susceptibility was less consistent, emphasizing the need for enlarging molecular epidemiologic studies to independent trials from different populations. The authors analyzed in North Portugal the association between variations at the two MTHFR positions and risk of ALL by comparing genotypes and gene frequencies in 103 affected children with those in 111 healthy controls. None of the variations was found to significantly affect the risk of developing childhood ALL in North Portugal, and this finding per se is of relevance in further studies aimed at assessing the etiology of the pathology in this specific population. Despite the absence of statistical significance, these data revealed that the frequency of MTHFR677T was lower in patients than in controls, a result that is congruent with other reports and with the functional model usually invoked to explain its ALL protective effect. Concerning MTHFR1298C, this study failed to corroborate previous findings of decreased risk of ALL in the presence of the variant.
亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢以及DNA甲基化与合成过程中的一种关键酶。此前已有研究探讨了MTHFR基因上两个常见的多态性位点C677T和A1298C在儿童或成人急性淋巴细胞白血病（ALL）病因学中的作用。尽管有系统报道称MTHFR677T对ALL具有保护作用，但其作用程度似乎受特定人群基因-环境相互作用的影响。关于MTHFR1298C在ALL易感性中作用的证据不太一致，这凸显了扩大分子流行病学研究至来自不同人群的独立试验的必要性。作者在葡萄牙北部通过比较103名患病儿童与111名健康对照的基因型和基因频率，分析了MTHFR两个位点的变异与ALL风险之间的关联。未发现任何变异会显著影响葡萄牙北部儿童患ALL的风险，这一发现本身对于进一步评估该特定人群中该疾病的病因学研究具有重要意义。尽管缺乏统计学意义，但这些数据显示患者中MTHFR677T的频率低于对照组，这一结果与其他报道以及通常用于解释其对ALL保护作用的功能模型相一致。关于MTHFR1298C，本研究未能证实此前关于该变体存在时ALL风险降低的研究结果。
