Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia.

Leukemia Research and Treatment Pub Date : 2012-01-01 Epub Date: 2012-10-17 DOI:10.1155/2012/292043
Dayse Maria Vasconcelos de Deus, Elker Lene Santos de Lima, Rafaela Maria Seabra Silva, Edinalva Pereira Leite, Maria Tereza Cartaxo Muniz
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引用次数: 35

Abstract

The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX) has been studied mainly in acute lymphoblastic leukemia (ALL) of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients (n = 126) with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive) of 0.36 for the 677CC genotype, corresponding also to lower overall survival (P = 0.0013); on the other hand, the 677TT genotype showed a better survival (98%). Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX (P < 0.0001).

Abstract Image

Abstract Image

亚甲基四氢叶酸还原酶C677T、A1298C和G80A多态性对急性淋巴细胞白血病患儿生存的影响
基因多态性对甲氨蝶呤(MTX)等化疗药物代谢的影响主要在儿童急性淋巴细胞白血病(ALL)中进行了研究。治疗的进步可能归因于化疗方案中增加的预后因素的识别。本研究的目的是分析C677T、A1298C和G80A多态性与MTHFR基因的关系,以及根据巴西方案接受MTX治疗的淋巴细胞白血病儿童患者(n = 126) 187个月的总生存率。C677T和G80A多态性采用PCR- rflp分型,A1298C多态性采用等位基因特异性PCR分型。我们观察到,677CC基因型ALL患者的死亡/存活率为0.36,也对应于较低的总生存率(P = 0.0013);另一方面,677TT基因型的存活率更高(98%)。因此,我们认为80AA基因型患者血浆MTX水平有小幅下降,提示携带80AA基因型的ALL儿童对MTX具有高毒性(P < 0.0001)。
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