亚甲基四氢叶酸还原酶（MTHFR）和硫嘌呤甲基转移酶（TPMT）基因与墨西哥儿童急性淋巴细胞白血病（ALL）易感性的关系。

Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans.

作者信息

Gutiérrez-Álvarez Ossyneidee, Lares-Asseff Ismael, Galaviz-Hernández Carlos, Reyes-Espinoza Elio-Aarón, Almanza-Reyes Horacio, Sosa-Macías Martha, Chairez Hernández Isaías, Salas-Pacheco José-Manuel, Bailón-Soto Claudia E

出版信息

Drug Metab Pers Ther. 2016 Mar;31(1):41-6. doi: 10.1515/dmpt-2015-0036.

DOI:10.1515/dmpt-2015-0036

PMID:26845729

Abstract

BACKGROUND

Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. Deviations in the folate flux resulting from single-nucleotide polymorphisms in genes encoding folate-dependent enzymes may affect the susceptibility to leukemia. This case-control study aimed to assess associations among MTHFR (C677T, A1298C) and TPMT (*2, *3A) mutations as well as to evaluate the synergistic effects of combined genotypes for both genes. Therefore, these genetic variants may lead to childhood acute lymphoblastic leukemia (ALL) susceptibility, in a Mexican population study.

METHODS

DNA samples obtained from 70 children with ALL and 152 age-matched controls (range, 1-15 years) were analyzed by real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect MTHFR C677T and A1298C and TPMT2 and TPMT3A genotypes.

RESULTS

The frequency of the MTHFR A1298C CC genotype was statistically significant (odds ratio [OR], 6.48; 95% 95% confidence intervals [CI], 1.26-33.2; p=0.025). In addition, the combined 677CC+1298AC genotype exhibited a statistically significant result (OR, 0.23; 95% CI, 0.06-0.82; p=0.023). No significant results were obtained from the MTHFR (C677T CT, C677T TT) or TPMT (*2, *3A) genotypes. More importantly, no association between the synergistic effects of either gene (MTHFR and/or TPMT) and susceptibility to ALL was found.

CONCLUSIONS

The MTHFR A1298C CC genotype was associated with an increased risk of developing childhood ALL. However, a decreased risk to ALL with the combination of MTHFR 677CC+1298AC genotypes was found.

摘要

背景

叶酸代谢在DNA合成和甲基化过程中起着至关重要的作用。编码叶酸依赖性酶的基因中的单核苷酸多态性导致的叶酸通量偏差可能会影响白血病的易感性。这项病例对照研究旨在评估亚甲基四氢叶酸还原酶（MTHFR，C677T、A1298C）和硫嘌呤甲基转移酶（TPMT，*2、*3A）突变之间的关联，并评估两种基因联合基因型的协同效应。因此，在一项墨西哥人群研究中，这些基因变异可能导致儿童急性淋巴细胞白血病（ALL）易感性。

方法

通过实时逆转录聚合酶链反应（RT-qPCR）分析从70例ALL患儿和152例年龄匹配的对照者（年龄范围1至15岁）获得的DNA样本，以检测MTHFR C677T和A1298C以及TPMT2和TPMT3A基因型。

结果

MTHFR A1298C CC基因型的频率具有统计学意义（优势比[OR]，6.48；95%置信区间[CI]，1.26 - 33.2；p = 0.025）。此外，联合的677CC + 1298AC基因型呈现出具有统计学意义的结果（OR，0.23；95% CI，0.06 - 0.82；p = 0.023）。MTHFR（C677T CT、C677T TT）或TPMT（*2、*3A）基因型未获得显著结果。更重要的是，未发现任何一个基因（MTHFR和/或TPMT）的协同效应与ALL易感性之间存在关联。