Gómez-Gómez Yazmín, Organista-Nava Jorge, Saavedra-Herrera Mónica Virginia, Rivera-Ramírez Ana Bertha, Terán-Porcayo Marco Antonio, Del Carmen Alarcón-Romero Luz, Illades-Aguiar Berenice, Leyva-Vázquez Marco Antonio
Laboratories of Molecular Biomedicine, and.
Exp Ther Med. 2012 Apr;3(4):665-672. doi: 10.3892/etm.2012.447. Epub 2012 Jan 9.
Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key component in childhood acute lymphoblastic leukemia (ALL) treatment. Polymorphisms in the gene coding for DHFR have been associated with adverse event treatment. This study evaluated the effect of the -A317G and C829T polymorphisms in the DHFR gene on survival and risk of relapse of ALL. Seventy patients with ALL and 100 healthy individuals were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. An association between the polymorphisms and the risk of relapse was found (p<0.05); patients with the -317G/G genotype were found to have an 8.55 (95% CI 1.84-39.70) higher chance of relapse and carriers of the 829T/T genotype had a 14.0 (95% CI 1.13-172.63) higher chance of relapse. Other variables, such as age and leukocyte count, were associated (p<0.05) with the risk of relapse of the disease. Individuals with the G/G and T/T genotype of the -A317G and C829T polymorphisms had poorer survival compared to other genotype groups (log-rank test; p<0.05). Although preliminary, these data seem to suggest a role for the DHFR polymorphisms in the risk of relapse of ALL and the mortality risk in these patients.
二氢叶酸还原酶（DHFR）是甲氨蝶呤的主要作用靶点，甲氨蝶呤是儿童急性淋巴细胞白血病（ALL）治疗中的关键成分。编码DHFR的基因多态性与不良事件治疗相关。本研究评估了DHFR基因中-A317G和C829T多态性对ALL患者生存和复发风险的影响。采用聚合酶链反应-限制性片段长度多态性方法对70例ALL患者和100名健康个体进行基因分型。发现多态性与复发风险之间存在关联（p<0.05）；-317G/G基因型患者的复发几率高出8.55倍（95%可信区间1.84-39.70），829T/T基因型携带者的复发几率高出14.0倍（95%可信区间1.13-172.63）。其他变量，如年龄和白细胞计数，与疾病复发风险相关（p<0.05）。与其他基因型组相比，-A317G和C829T多态性的G/G和T/T基因型个体的生存率较差（对数秩检验；p<0.05）。尽管这些数据是初步的，但似乎表明DHFR多态性在ALL复发风险和这些患者的死亡风险中起作用。
