Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to pediatric acute lymphoblastic leukemia in a German study population.
Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to pediatric acute lymphoblastic leukemia in a German study population.
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DOI：
10.1186/1471-2350-6-23
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发表时间：
2005-05-27
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亚甲基四氢叶酸还原酶(MTHFR)在5，10-亚甲基四氢叶酸(亚甲基-四氢叶酸)转化为5-甲基-四氢叶酸(5-甲基-四氢叶酸)的叶酸途径调节中起着重要作用。MTHFR基因的两个常见的多态(677C和GT；T和1298A和GT；C)被证明降低了MTHFR酶的活性，并与血管疾病、神经管缺陷和淋巴系统恶性肿瘤等不同疾病的易感性有关。关于这些多态在急性淋巴细胞白血病(ALL)易感性中的作用的研究导致了不同的结果。我们通过对连续参加德国多中心试验ALL-BFM2000的443名ALL患者和379名健康对照的研究样本进行基因分型，对MTHFR 677C和1298A；T和1298A；C基因多态与儿童ALL的相关性进行了回顾性评估。我们计算了基于MTHFR 677C>；T和1298A>；C多态的MTHFR基因型的优势比，以检查这两个多态中的一个或两个是否与儿童ALL相关。无论是在全部患者组中，还是在按性别、确诊年龄、DNA指数、免疫表型或TEL/AML1重排分层的分析中，都没有观察到特定的MTHFR变异或变异组合与ALL风险之间的显著关联。我们的发现表明，MTHFR 677C>；T和1298A>；C基因变异对德国人群中儿童ALL的易感性没有重大影响。
Methylenetetrahydrofolate reductase (MTHFR) has a major impact on the regulation of the folic acid pathway due to conversion of 5,10-methylenetetrahydrofolate (methylene-THF) to 5-methyl-THF. Two common polymorphisms (677C>T and 1298A>C) in the gene coding for MTHFR have been shown to reduce MTHFR enzyme activity and were associated with the susceptibility to different disorders, including vascular disease, neural tube defects and lymphoid malignancies. Studies on the role of these polymorphisms in the susceptibility to acute lymphoblastic leukemia (ALL) led to discrepant results. We retrospectively evaluated the association of the MTHFR 677C>T and 1298A>C polymorphisms with pediatric ALL by genotyping a study sample of 443 ALL patients consecutively enrolled onto the German multicenter trial ALL-BFM 2000 and 379 healthy controls. We calculated odds ratios of MTHFR genotypes based on the MTHFR 677C>T and 1298A>C polymorphisms to examine if one or both of these polymorphisms are associated with pediatric ALL. No significant associations between specific MTHFR variants or combinations of variants and risk of ALL were observed neither in the total patient group nor in analyses stratified by gender, age at diagnosis, DNA index, immunophenotype, or TEL/AML1 rearrangement. Our findings suggest that the MTHFR 677C>T and 1298A>C gene variants do not have a major influence on the susceptibility to pediatric ALL in the German population.